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1.  Early sex differences are not autism-specific: A Baby Siblings Research Consortium (BSRC) study 
Molecular Autism  2015;6:32.
The increased male prevalence of autism spectrum disorder (ASD) may be mirrored by the early emergence of sex differences in ASD symptoms and cognitive functioning. The female protective effect hypothesis posits that ASD recurrence and symptoms will be higher among relatives of female probands. This study examined sex differences and sex of proband differences in ASD outcome and in the development of ASD symptoms and cognitive functioning among the high-risk younger siblings of ASD probands and low-risk children.
Prior to 18 months of age, 1824 infants (1241 high-risk siblings, 583 low-risk) from 15 sites were recruited. Hierarchical generalized linear model (HGLM) analyses of younger sibling and proband sex differences in ASD recurrence among high-risk siblings were followed by HGLM analyses of sex differences and group differences (high-risk ASD, high-risk non-ASD, and low-risk) on the Mullen Scales of Early Learning (MSEL) subscales (Expressive and Receptive Language, Fine Motor, and Visual Reception) at 18, 24, and 36 months and Autism Diagnostic Observation Schedule (ADOS) domain scores (social affect (SA) and restricted and repetitive behaviors (RRB)) at 24 and 36 months.
Of 1241 high-risk siblings, 252 had ASD outcomes. Male recurrence was 26.7 % and female recurrence 10.3 %, with a 3.18 odds ratio. The HR-ASD group had lower MSEL subscale scores and higher RRB and SA scores than the HR non-ASD group, which had lower MSEL subscale scores and higher RRB scores than the LR group. Regardless of group, males obtained lower MSEL subscale scores, and higher ADOS RRB scores, than females. There were, however, no significant interactions between sex and group on either the MSEL or ADOS. Proband sex did not affect ASD outcome, MSEL subscale, or ADOS domain scores.
A 3.2:1 male:female odds ratio emerged among a large sample of prospectively followed high-risk siblings. Sex differences in cognitive performance and repetitive behaviors were apparent not only in high-risk children with ASD, but also in high-risk children without ASD and in low-risk children. Sex differences in young children with ASD do not appear to be ASD-specific but instead reflect typically occurring sex differences seen in children without ASD. Results did not support a female protective effect hypothesis.
Electronic supplementary material
The online version of this article (doi:10.1186/s13229-015-0027-y) contains supplementary material, which is available to authorized users.
PMCID: PMC4455973  PMID: 26045943
Sex differences; High-risk siblings; Symptom severity; Development; Longitudinal
2.  Cognitive Behavioral Therapy, Sertraline, or a Combination in Childhood Anxiety 
The New England journal of medicine  2008;359(26):2753-2766.
Anxiety disorders are common psychiatric conditions affecting children and adolescents. Although cognitive behavioral therapy and selective serotonin-reuptake inhibitors have shown efficacy in treating these disorders, little is known about their relative or combined efficacy.
In this randomized, controlled trial, we assigned 488 children between the ages of 7 and 17 years who had a primary diagnosis of separation anxiety disorder, generalized anxiety disorder, or social phobia to receive 14 sessions of cognitive behavioral therapy, sertraline (at a dose of up to 200 mg per day), a combination of sertraline and cognitive behavioral therapy, or a placebo drug for 12 weeks in a 2:2:2:1 ratio. We administered categorical and dimensional ratings of anxiety severity and impairment at baseline and at weeks 4, 8, and 12.
The percentages of children who were rated as very much or much improved on the Clinician Global Impression-Improvement scale were 80.7% for combination therapy (P<0.001), 59.7% for cognitive behavioral therapy (P<0.001), and 54.9% for sertraline (P<0.001); all therapies were superior to placebo (23.7%). Combination therapy was superior to both monotherapies (P<0.001). Results on the Pediatric Anxiety Rating Scale documented a similar magnitude and pattern of response; combination therapy had a greater response than cognitive behavioral therapy, which was equivalent to sertraline, and all therapies were superior to placebo. Adverse events, including suicidal and homicidal ideation, were no more frequent in the sertraline group than in the placebo group. No child attempted suicide. There was less insomnia, fatigue, sedation, and restlessness associated with cognitive behavioral therapy than with sertraline.
Both cognitive behavioral therapy and sertraline reduced the severity of anxiety in children with anxiety disorders; a combination of the two therapies had a superior response rate. ( number, NCT00052078.)
PMCID: PMC2702984  PMID: 18974308
3.  Cognitive outcomes and familial stress after cochlear implantation in deaf children with and without developmental delays 
The benefits of cochlear implantation for children with developmental delays (DD) are often unclear. We compared cognition, adaptive behavior, familial stress, and communication in children with and without DD.
Study Design
Retrospective review
Two tertiary care pediatric hospitals
204 children who underwent cochlear implantation assessed before and >1 year after implantation
Main Outcome Measures
The Mullen Scales of Early Learning (MSEL), Vineland Adaptive Behavior Scales (VABS), Parental Stress Index (PSI), and Preschool Language Scale (PLS).
We developed a specific definition of DD for hearing-impaired children based upon DSM-IV criteria for mental retardation; 60 children met the criteria for DD and 144 children did not. Prior to implantation, multiple linear regression demonstrated that children with DD had lower scores in every domain of the MSEL and VABS (p<0.05) but no differences in any domains of the PSI and PLS (p>0.1) compared to children without DD. After implantation, children without DD demonstrated significant improvements in intelligence as measured by the MSEL, age-appropriate improvements in adaptive behavior as evaluated by the VABS, and their familial stress levels were not increased after cochlear implantation. In contrast, children with DD underwent implantation at a later age and demonstrated less comprehensive developmental improvements after cochlear implantation and higher stress levels. However, when the age differences were taken into account using multiple linear regression analyses, the differences between two cohorts were reduced.
These data indicate that our definition of DD is a reliable method of stratifying deaf children. While children with DD have a normal developmental rate of adaptive behavior after cochlear implantation, their developmental rate of intelligence is lower and they have higher stress levels than children without DD. However, our data suggest that if children with DD could be implanted as early as children without DD, their intelligence and stress outcomes would be improved.
PMCID: PMC3399955  PMID: 22710555
4.  Clinical outcomes of an early intervention program for preschool children with Autism Spectrum Disorder in a community group setting 
BMC Pediatrics  2013;13:3.
Available evidence indicates that early intervention programs, such as the Early Start Denver Model (ESDM), can positively affect key outcomes for children with Autism Spectrum Disorder (ASD). However, programs involving resource intensive one-to-one clinical intervention are not readily available or deliverable in the community, resulting in many children with ASD missing out on evidence-based intervention during their early and most critical preschool years. This study evaluated the effectiveness of the ESDM for preschool-aged children with ASD using a predominantly group-based intervention in a community child care setting.
Participants were 26 children (21 male) with ASD with a mean age of 49.6 months. The ESDM, a comprehensive early intervention program that integrates applied behaviour analysis with developmental and relationship-based approaches, was delivered by trained therapists during the child’s attendance at a child care centre for preschool-aged children with ASD. Children received 15–20 hours of group-based, and one hour of one-to-one, ESDM intervention per week. The average intervention period was ten months. Outcome measures were administered pre- and post-intervention, and comprised a developmental assessment - the Mullen Scales of Early Learning (MSEL); and two parent-report questionnaires - the Social Communication Questionnaire (SCQ) and Vineland Adaptive Behaviours Scales–Second Edition (VABS-II).
Statistically significant post-intervention improvements were found in children’s performance on the visual reception, receptive language and expressive language domains of the MSEL in addition to their overall intellectual functioning, as assessed by standardised developmental quotients. Parents reported significant increases in their child’s receptive communication and motor skills on the VABS-II, and a significant decrease in autism-specific features on the SCQ. These effects were of around medium size, and appeared to be in excess of what may have been expected due to maturation. Nonetheless, these results need to be confirmed in a controlled study.
This study suggests community dissemination of the ESDM using predominantly group-based intervention may be an effective intervention. Making the ESDM accessible to the wider ASD community in child care settings has the potential for significant clinical and economic benefits. Further studies are indicated in this area, including those with younger children, and which incorporate a control group and standardised ASD assessments.
Trial registration
This trial is registered with the Australian New Zealand Clinical Trials Registry: Registry number ACTRN12612000461897.
PMCID: PMC3631131  PMID: 23294523
Autism; Behavioral intervention; Early intervention; Cognitive function; Developmental outcomes
5.  Treatment of functional dyspepsia with sertraline: A double-blind randomized placebo-controlled pilot study 
AIM: To evaluate sertraline, a selective serotonin reuptake inhibitor in the treatment of patients with functional dyspepsia.
METHODS: Consecutive tertiary hospital patients with a clinical diagnosis of functional dyspepsia (FD) according to the Rome II criteria with a Hong Kong dyspepsia index (HKDI) of greater than 16 were recruited. Patients commenced enrolment prior to the inception of the Rome III criteria for functional dyspepsia. All patients were ethnic Chinese, had a normal upper endoscopy and were Helicobacter pylori negative prior to enrolment. Study patients were randomized to receive sertraline 50 mg or placebo daily for 8 wk. HKDI symptom scores, quality of life, hospital anxiety and depression (HAD) scale and global symptom relief were evaluated before, during and after treatment. Adverse effects were monitored during and after treatment.
RESULTS: A total of 193 patients were randomized in the intention to treat (ITT), and 150 patients were included in the per protocol (PP) analysis. In both the ITT and PP, there was no difference in the primary outcome of global dyspepsia symptoms between the sertraline and placebo groups at week 8. In the ITT analysis, 98 and 95 patients were randomized to the sertraline and placebo groups respectively. A total of 43 patients withdrew from the study (22.3%) by week 8, with 23 of the 24 drop-outs in the sertraline group occurring prior to week 4 (95.8%). In contrast, in the placebo arm, 11 of 19 patients dropped out by week 4 (57.9%). Utilizing the last response carried forward to account for the drop-outs, there were no differences between the sertraline and placebo groups at baseline in terms of the HKDI, HKDI 26.08 ± 6.19 vs 26.70 ± 5.89, P = 0.433; and at week 8, HKDI 22.41 ± 6.36 vs 23.25 ± 7.30, P = 0.352 respectively. In the PP analysis, 74 and 76 patients were randomized to the sertraline and placebo groups respectively. At baseline, there were no statistically significant differences between the sertraline and placebo groups, HKDI 25.83 ± 6.313 vs 27.19 ± 5.929 respectively, P = 0.233; however by week 8, patients in the sertraline group demonstrated a statistically significant difference in their Hong Kong Dyspepsia Index compared to placebo, HKDI 20.53 ± 6.917 vs 23.34 ± 7.199, P = 0.02, respectively). There was also no statistically significant difference in overall quality of life measures or the HAD scale related to treatment in either the ITT or PP analysis at week 8.
CONCLUSION: This pilot study, the first to examine sertraline, a selective serotonin reuptake inhibitor, for the management of FD, did not find that it was superior to placebo.
PMCID: PMC3496890  PMID: 23155342
Dyspepsia; Chinese; Gastrointestinal diseases; Drug therapy; Sertraline; Selective serotonin re-uptake inhibitors
6.  The response to sertraline in men with chronic pelvic pain syndrome 
Sexually Transmitted Infections  2005;81(2):147-149.
Objectives: Male chronic pelvic pain syndrome (CPPS) is difficult to manage. Although antidepressants are frequently used in clinical practice, to date no interventional study has been published. We investigated men with CPPS to assess their response to the serotonin specific reuptake inhibitor (SSRI) antidepressant, sertraline.
Methods: Men with CPPS underwent a four glass test to exclude an infective cause for their symptoms. They were randomised to sertraline or matched placebo for 13 weeks after which they were unblinded. They were then allowed to either continue sertraline or cross over to active treatment for a further 13 weeks. Prostatic symptom severity (PSS) and frequency (PSF) scores, the Hospital Anxiety and Depression (HAD) scale and a psychosexual (PSex) questionnaire were completed at 0, 6, 13, and 26 weeks. Statistical analysis was by the Mann-Whitney U and Wilcoxon signed rank tests.
Results: 14 men enrolled. At week 13 there was a mean reduction in PSS scores of 6.1 in the active and 2.0 in placebo group, and in PSF scores of 3.6 and 1.0, respectively. There was no statistically significant difference in the PSS and PSF scores between the active versus placebo group because of the small subject numbers. If analysed as a case series, there was a significant reduction in PSS (11.7; p = 0.01) and PSF (5.9; p = 0.03) from baseline following 13 weeks of sertraline. There was also a decrease in mean HAD depression score from 4.6 at baseline to 2.4.
Conclusion: Sertraline led to a significant improvement in prostatic symptom severity and frequency from baseline following 13 weeks of treatment. Although this analysis does not exclude a placebo effect, the randomised placebo controlled findings show a trend to improvement with sertraline when compared to placebo.
PMCID: PMC1764675  PMID: 15800093
7.  Social anxiety disorder: radio electric asymmetric conveyor brain stimulation versus sertraline 
Social anxiety disorder (SAD) is a disabling condition that affects almost 5% of the general population. Many types of drugs have shown their efficacy in the treatment of SAD. There are also some data regarding psychotherapies, but no data are available today about the efficacy of brain stimulation techniques. The aim of the study is to compare the efficacy of noninvasive brain stimulation neuro psycho physical optimization (NPPO) protocol performed by radio electric asymmetric conveyor (REAC) with that of sertraline in adults with SAD.
Patients and methods
Twenty SAD patients on sertraline were compared with 23 SAD patients who refused any drug treatment and who chose to be treated with NPPO-REAC brain stimulation. This was a 6-month, open-label, naturalistic study. Patients on sertraline received flexible doses, whereas NPPO-REAC patients received two 18-session cycles of treatment. Clinical Global Improvement scale items “much improved” or “very much improved” and Liebowitz Social Anxiety Scale total score variation on fear and avoidance components were used to detect the results. The statistical analysis was performed with t-test. All measures <0.05 have been considered statistically significant.
Ten of 23 subjects on NPPO-REAC and six of the 20 taking sertraline were much improved or very much improved 1 month after the first NPPO-REAC cycle (t1). Sixteen of the subjects on NPPO-REAC and ten of the subjects taking sertraline were much improved or very much improved 1 month after the second NPPO-REAC cycle (t2). In respect of the Liebowitz Social Anxiety Scale, at t1 NPPO-REAC resulted in statistically more efficacy for sertraline on both fear and avoidance total scores. At t2, NPPO-REAC resulted in statistically more efficacy for sertraline on fear but not on avoidance.
NPPO-REAC is an effective treatment for SAD, allowing substantial and clinically meaningful reductions in symptoms and disability in comparison with sertraline.
PMCID: PMC3234900  PMID: 22163157
social anxiety disorder; brain stimulation; REAC; sertraline; fear; avoidance
8.  Sertraline versus other antidepressive agents for depression 
The National Institute for Health and Clinical Excellence clinical practice guideline on the treatment of depressive disorder recommended that selective serotonin reuptake inhibitors should be the first-line option when drug therapy is indicated for a depressive episode. Preliminary evidence suggested that sertraline might be slightly superior in terms of effectiveness.
To assess the evidence for the efficacy, acceptability and tolerability of sertraline in comparison with tricyclics (TCAs), heterocyclics, other SSRIs and newer agents in the acute-phase treatment of major depression.
Search methods
MEDLINE (1966 to 2008), EMBASE (1974 to 2008), the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register and the Cochrane Central Register of Controlled Trials up to July 2008. No language restriction was applied. Reference lists of relevant papers and previous systematic reviews were hand-searched. Pharmaceutical companies and experts in this field were contacted for supplemental data.
Selection criteria
Randomised controlled trials allocating patients with major depression to sertraline versus any other antidepressive agent.
Data collection and analysis
Two review authors independently extracted data. Discrepancies were resolved with another member of the team. A double-entry procedure was employed by two reviewers. Information extracted included study characteristics, participant characteristics, intervention details and outcome measures in terms of efficacy (the number of patients who responded or remitted), acceptability (the number of patients who failed to complete the study) and tolerability (side-effects).
Main results
A total of 59 studies, mostly of low quality, were included in the review, involving multiple treatment comparisons between sertraline and other antidepressant agents. Evidence favouring sertraline over some other antidepressants for the acute phase treatment of major depression was found, either in terms of efficacy (fluoxetine) or acceptability/tolerability (amitriptyline, imipramine, paroxetine and mirtazapine). However, some differences favouring newer antidepressants in terms of efficacy (mirtazapine) and acceptability (bupropion) were also found. In terms of individual side effects, sertraline was generally associated with a higher rate of participants experiencing diarrhoea.
Authors’ conclusions
This systematic review and meta-analysis highlighted a trend in favour of sertraline over other antidepressive agents both in terms of efficacy and acceptability, using 95% confidence intervals and a conservative approach, with a random effects analysis. However, the included studies did not report on all the outcomes that were pre-specified in the protocol of this review. Outcomes of clear relevance to patients and clinicians were not reported in any of the included studies.
PMCID: PMC4163971  PMID: 20393946
Antidepressive Agents [adverse effects; *therapeutic use]; Depression [*drug therapy]; Diarrhea [chemically induced]; Randomized Controlled Trials as Topic; Serotonin Uptake Inhibitors [adverse effects; *therapeutic use]; Sertraline [adverse effects; *therapeutic use]; Treatment Outcome; Humans
9.  Change in Cognitive Functioning in Depressed Older Adults Following Treatment with Sertraline or Nortriptyline 
To compare the impact of nortriptyline to sertraline on change in cognitive functioning in depressed older adults.
We used pre-post neuropsychological data collected as part of a 12-week medication trial comparing sertraline to nortriptyline in the treatment of older adults with non-psychotic, unipolar major depression to examine change in cognitive functioning. Neuropsychological assessments included mental status (Mini-Mental Status Exam), psychomotor speed (Purdue Pegboard), attention (Continuous Performance Test; Trail Making Test A), executive functioning (Stroop Color/Word Test; Trail Making Test B), and memory (Buschke Selective Reminding Test).
Within treatment groups, patients treated with sertraline improved only on verbal learning. This change did not depend on responder status. Between treatment groups, patients treated with sertraline improved more in verbal learning compared to patients treated with nortriptyline. Looking at change in cognition as a function of medication condition and responder status revealed that sertraline responders improved more in verbal learning compared to nortriptyline responders but not more than sertraline non-responders or nortriptyline non-responders. Nortriptyline responders were the only treatment by responder status group to show no improvement in verbal learning from baseline to endpoint.
Unexpectedly, nortriptyline responders showed no improvement in verbal learning as compared to patients treated with sertraline or nortriptyline non-responders. However, given the small sample sizes and number of statistical tests (potential for type 1 error), replication is warranted.
PMCID: PMC3391314  PMID: 21919060
cognitive functioning; cognitive impairment; depression; nortriptyline; sertraline
10.  A Randomized, Placebo-Controlled, Double-Blind Trial of Sertraline for Postpartum Depression 
Psychopharmacology  2013;231(5):939-948.
Postpartum depression (PMD) occurs in roughly 10% of postpartum women and negatively impacts the mother and her offspring, but there are few placebo-controlled studies of antidepressant treatment in this population.
To compare the selective serotonin reuptake inhibitor (SSRI) sertraline to placebo for treating PMD.
This was a single-center, 6-week, randomized double-blind placebo-controlled trial of sertraline with a one-week placebo lead-in. Participants (n=38) were women with depression onset within 3 months of delivery; a subset (n=27) met strict DSM-IV criteria for PMD (onset within 4 weeks of delivery). Participants were prescribed sertraline 50 mg or placebo daily, to a maximum of 200 mg/day. Primary outcome variables were the Hamilton Depression Rating Scale (HAM-D) and Clinical Global Impressions (CGI) scores, which were used to determine rates of response and remission.
Sertraline produced a significantly greater response rate (59%) than placebo (26%) and a more than 2-fold increased remission rate (53% vs. 21%). Mixed models did not reveal significant group by time effects, although in the subset of women who met DSM-IV criteria, there was a statistically significant group by time effect for the HAM-D, Hamilton Anxiety Rating Scale (HAM-A) and CGI.
Women with PMD are more likely to have a remission of their depression with sertraline treatment, a finding that is more pronounced in women who have onset of depression within 4 weeks of childbirth. These data support the continued use of 4 weeks for the DSM-5 postpartum onset specifier for major depressive disorder.
PMCID: PMC3945214  PMID: 24173623
postpartum; puerperal; depression; sertraline; SSRI; pregnancy; women
11.  Early sensory over-responsivity in toddlers with autism spectrum disorders as a predictor of family impairment and parenting stress 
Sensory over-responsivity (SOR) affects many individuals with autism spectrum disorders (ASD), often leading to stressful encounters during daily routines.
This study describes the associations between early SOR symptoms and the longitudinal course of restrictions in family life activities and parenting stress across three time points in families raising a child with ASD (n = 174). Covariates were child diagnostic severity, emotional problems, and maternal affective symptoms. At time 1 mean chronological age was 28.5 months. Children were administered the Autism Diagnostic Observation Schedule (ADOS) and Mullen Scales of Early Learning (MSEL). Parents completed the Infant Toddler Sensory Profile (ITSP), Infant Toddler Social Emotional Assessment (ITSEA), Beck Anxiety Index (BAI), and the Center for Epidemiologic Studies Depression Inventory (CES-D) at time 1; and the Parenting Stress Index (PSI) and Family Life Impairment Scale (FLIS) at the three annual time points.
Latent Growth Curve Models indicated that higher SOR scores on the ITSP at time 1 were associated with higher initial levels of family life impairment and parenting stress and with a smaller magnitude of change over time. These associations were independent of severity of ADOS social-communication symptoms, MSEL composite score, ITSEA externalizing and anxiety symptoms, and maternal affective symptoms as measured by the BAI and CES-D. On average FLIS and PSI did not change over time however there was significant individual variability. Concurrently, SOR at time 1 explained 39–45% of the variance in family stress and impairment variables.
An evaluation of SOR should be integrated into the assessment of toddlers with ASD considering their role in family life impairment and stress.
PMCID: PMC3636173  PMID: 23336424
ASD; toddlers; sensory over-responsivity; family impairment; parenting stress
12.  Safety and Efficacy of Sertraline for Depression in Patients With Heart Failure: Results of the SADHART-CHF Trial 
The objective was to test the hypothesis that heart failure (HF) patients treated with sertraline will have lower depression scores and fewer cardiovascular events compared to placebo.
Depression is common among HF patients. It is associated with increased hospitalization and mortality.
SADHART-CHF was a randomized, double-blind, placebo-controlled trial of sertraline 50 to 200 mg/day versus matching placebo for 12 weeks. All participants also received nurse facilitated support. Eligible patients were age ≥45 years with HF (LVEF ≤45%, NYHA class II-IV) and clinical depression (DSM-IV criteria for current major depressive disorder). Significant cognitive impairment, psychosis, recent alcohol or drug dependence, bipolar or severe personality disorder, active suicidal ideation, and current antipsychotic or antidepressant medications were exclusions. Primary endpoints were change in depression severity (Hamilton Depression Rating Scale [HDRS] total score) and composite cardiovascular status at12-weeks.
469 patients were randomized (N=234 sertraline, N=235 placebo). The mean ± SE change from baseline to 12-weeks in the HDRS total score was -7.1 ± 0.5 (sertraline) and -6.8 ± 0.5 (placebo) (P<.001 from baseline, P=.89 between groups, mean change between groups -0.4, 95% CI -1.7, 0.92). The proportion whose composite cardiovascular score worsened, improved, or was unchanged was 29.9%, 40.6%, and 29.5% in the sertraline group and 31.1%, 43.8%, and 25.1% in the placebo group (P=0.78).
Sertraline was safe in patients with significant HF. However, treatment with sertraline compared with placebo did not provide greater reduction in depression or improved cardiovascular status among patients with HF and depression.
PMCID: PMC3663330  PMID: 20723799
heart failure; depression
13.  Randomized, Placebo-Controlled Trial of Cognitive-Behavioral Therapy Alone or Combined with Sertraline in the Treatment of Pediatric Obsessive-Compulsive Disorder 
Behaviour research and therapy  2013;51(12):823-829.
To examine the efficacy of sequential sertraline and cognitive-behavioral therapy (CBT) treatment relative to CBT with pill placebo over 18 weeks in children and adolescents with obsessive-compulsive disorder (OCD).
Forty-seven children and adolescents with OCD (Range=7-17 years) were randomized to 18-weeks of treatment in one of three arms: 1) sertraline at standard dosing + CBT (RegSert+CBT); 2) sertraline titrated slowly but achieving at least 8 weeks on the maximally tolerated daily dose + CBT (SloSert+CBT); or 3) pill placebo + CBT (PBO+CBT). Assessments were conducted at screening, baseline, weeks 1-9, 13, and 17, and post- treatment. Raters and clinicians were blinded to sertraline (but not CBT) randomization status. Primary outcomes included the Children’s Yale-Brown Obsessive-Compulsive Scale, and response and remission status. Secondary outcomes included the Child Obsessive Compulsive Impact Scale–Parent/Child, Children’s Depression Rating Scale-Revised, Multidimensional Anxiety Scale for Children, and Clinical-Global Impressions-Severity.
All groups exhibited large within-group effects across outcomes. There was no group by time interaction across all outcomes suggesting that group changes over time were comparable.
Among youth with OCD, there was no evidence that sequentially provided sertraline with CBT differed from those receiving placebo with CBT.
PMCID: PMC3908957  PMID: 24184429
Obsessive-Compulsive Disorder; Children; Cognitive-Behavioral Therapy; Treatment; Sertraline
14.  Maternal Metabolic Conditions and Risk for Autism and Other Neurodevelopmental Disorders 
Pediatrics  2012;129(5):e1121-e1128.
We examined whether metabolic conditions (MCs) during pregnancy (diabetes, hypertension, and obesity) are associated with autism spectrum disorder (ASD), developmental delays (DD), or impairments in specific domains of development in the offspring.
Children aged 2 to 5 years (517 ASD, 172 DD, and 315 controls) were enrolled in the CHARGE (Childhood Autism Risks from Genetics and the Environment) study, a population-based, case-control investigation between January 2003 and June 2010. Eligible children were born in California, had parents who spoke English or Spanish, and were living with a biological parent in selected regions of California. Children’s diagnoses were confirmed by using standardized assessments. Information regarding maternal conditions was ascertained from medical records or structured interview with the mother.
All MCs were more prevalent among case mothers compared with controls. Collectively, these conditions were associated with a higher likelihood of ASD and DD relative to controls (odds ratio: 1.61 [95% confidence interval: 1.10–2.37; odds ratio: 2.35 [95% confidence interval: 1.43–3.88], respectively). Among ASD cases, children of women with diabetes had Mullen Scales of Early Learning (MSEL) expressive language scores 0.4 SD lower than children of mothers without MCs (P < .01). Among children without ASD, those exposed to any MC scored lower on all MSEL and Vineland Adaptive Behavior Scales (VABS) subscales and composites by at least 0.4 SD (P < .01 for each subscale/composite).
Maternal MCs may be broadly associated with neurodevelopmental problems in children. With obesity rising steadily, these results appear to raise serious public health concerns.
PMCID: PMC3340592  PMID: 22492772
autism; developmental delay; diabetes; epidemiology; hypertension; obesity
15.  Poor Response to Sertraline in Methamphetamine Dependence is Associated with Sustained Craving for Methamphetamine 
Drug and alcohol dependence  2011;118(2-3):500-503.
Depression is common among individuals with methamphetamine (MA) use disorders. As agents that enhance serotonergic function are frequently used to treat depression, one might predict that they would be useful medications for MA dependence. However, clinical trials of serotonergic agents for MA addiction have been unsuccessful.
To identify factors that distinguish MA-dependent research participants who increased MA self-administration while receiving treatment with the selective serotonin reuptake inhibitor (SSRI) sertraline from other groups of participants.
Using a dataset from a 12-week randomized, placebo-controlled trial of sertraline (100 mg daily) for MA addiction, we identified participants who had completed at least 8 weeks of the trial (n=61 sertraline, n=68 placebo). We compared the proportions of MA-positive urine tests for weeks 8–12 of the trial for these subjects to their pre-randomization baseline, and identified those subjects who increased MA use during treatment. Using classification trees, we then assessed all data collected during the study to identify factors associated with increasing MA use during treatment with sertraline, compared to placebo.
More subjects in the sertraline condition increased MA use during treatment (n=13) than in the placebo condition (n=5; p=0.03). Classification trees identified multiple factors from both pre-treatment and in-treatment data that were associated with increased MA use during treatment. Only elevated in-treatment craving for MA specifically characterized subjects in the sertraline group who increased their MA use.
Some MA-abusing individuals treated with SSRIs have sustained craving with an increased propensity to relapse during treatment despite psychosocial treatment interventions.
PMCID: PMC3181284  PMID: 21592681
antidepressants; sertraline; methamphetamine; addiction; craving; classification and regression trees
16.  Combining Seeking Safety with Sertraline for PTSD and Alcohol Use Disorders: A Randomized Controlled Trial 
The current study marks the first randomized controlled trial to test the benefit of combining Seeking Safety (SS), a present-focused cognitive behavioral therapy for co-occurring posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD), with sertraline, a front-line medication for PTSD shown to also impact drinking outcomes.
Sixty-nine participants (81% female; 59% African American) with primarily childhood sexual (46%) and physical (39%) trauma exposure, and drug dependence in addition to AUD were randomized to receive a partial-dose (12 sessions) of SS with either sertraline (n = 32; M = 7 sessions) or placebo (n = 37; M = 6 sessions). Assessments conducted at baseline, end-of-treatment, 6- and 12-months posttreatment measured PTSD and AUD symptom severity.
Both groups demonstrated significant improvement in PTSD symptoms. The SS plus sertraline group exhibited a significantly greater reduction in PTSD symptoms than the SS plus placebo group at end-of-treatment (M difference = −16.15, p = .04, d = 0.83), which was sustained at 6- and 12-month follow-up (M difference = −13.81, p = .04, d = 0.71, and M difference = −12.72, p = .05, d = 0.65, respectively). Both SS groups improved significantly on AUD severity at all posttreatment time points with no significant differences between SS plus sertraline and SS plus placebo.
Results support the combining of a cognitive behavioral therapy and sertraline for PTSD/AUD. Clinically significant reductions in both PTSD and AUD severity were achieved and sustained through 12-months follow-up, Moreover, greater mean improvement in PTSD symptoms was observed across all follow-up assessments in the SS plus sertraline group.
PMCID: PMC4380540  PMID: 25622199
PTSD; alcohol abuse; cognitive-behavioral treatment; sertraline; selective serotonin reuptake inhibitor; randomized clinical trial
17.  Post-traumatic stress disorder 
BMJ Clinical Evidence  2010;2010:1005.
Post-traumatic stress disorder (PTSD) may affect 10% of women and 5% of men at some stage, and symptoms may persist for several years. Risk factors include major trauma, lack of social support, peritraumatic dissociation, and previous psychiatric history or personality factors.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent PTSD? What are the effects of interventions to treat PTSD? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2009 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
We found 46 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
In this systematic review we present information relating to the effectiveness and safety of the following interventions: affect management; antiepileptic drugs; antihypertensive drugs; benzodiazepines; brofaromine; CBT; drama therapy; eye movement desensitisation and reprocessing; fluoxetine; group therapy; hydrocortisone; hypnotherapy; inpatient treatment programmes; Internet-based psychotherapy; mirtazapine; multiple-session CBT; multiple-session collaborative trauma support; multiple-session education; nefazodone; olanzapine; paroxetine; phenelzine; psychodynamic psychotherapy; risperidone; SSRIs (versus other antidepressants); sertraline; single-session group debriefing; single-session individual debriefing; supportive psychotherapy; supportive counselling; temazepam; tricyclic antidepressants; and venlafaxine.
Key Points
Post-traumatic stress disorder (PTSD) is characterised by disabling symptoms of re-experiencing a traumatic event, avoidance behaviour, and hyperarousal (e.g., irritability or hypervigilance), lasting at least 1 month. PTSD may affect 10% of women and 5% of men at some stage, and symptoms may persist for several years.Risk factors include major trauma, lack of social support, peritraumatic dissociation, and previous psychiatric or personality factors.
Multiple-session trauma-focused CBT may be effective at preventing development of PTSD in people with psychological distress after a traumatic event. However, we don't know whether multiple-session trauma-focused CBT is beneficial for people who have experienced a traumatic event but have not been diagnosed with psychological distress.
We don't know whether antiepileptic drugs, antihypertensive drugs, hydrocortisone, multiple-session collaborative trauma support, multiple-session education, single-session group debriefing, or temazepam are beneficial in preventing PTSD. Single-session individual debriefing may increase the rate of PTSD after a traumatic event compared with no debriefing, and supportive counselling may be less effective than multiple-session CBT at preventing onset of PTSD.
In people with PTSD, trauma-focused CBT improves PTSD symptoms compared with no treatment or with other psychological interventions, including stress management and present-centred therapy. Eye movement desensitisation and reprocessing seems as effective as trauma-focused CBT in the treatment of chronic PTSD. We don't know whether other psychological treatments (affect management, drama therapy, group therapy, hypnotherapy, inpatient treatment regimens, Internet-based psychotherapy, psychodynamic psychotherapy, or supportive psychotherapy) are beneficial in people with PTSD.
Paroxetine may improve symptoms in people with PTSD. However, venlafaxine does not seem effective at improving symptoms, and the benefits of fluoxetine are unclear. We found insufficient good evidence to assess the effects of sertraline, tricyclic antidepressants, or benzodiazepines.We found limited evidence that sertraline and nefazodone may be equally effective at improving symptoms of PTSD, but we don't know how other antidepressants compare with each other in the treatment of PTSD.We don't know whether antiepileptic drugs, antihypertensive drugs, brofaromine, nefazodone, olanzapine, phenelzine, mirtazapine, or risperidone are beneficial in people with PTSD.
PMCID: PMC2907597  PMID: 21718580
18.  Sertraline plus deanxit to treat patients with depression and anxiety in chronic somatic diseases: a randomized controlled trial 
BMC Psychiatry  2015;15:84.
Patients in chronic somatic diseases are often accompanied with depression and anxiety, remission of which may be observed in the third or fourth week after applying common antidepressant medications. We investigate the efficacy and safety of sertraline plus deanxit on patients with depression and anxiety in chronic somatic diseases.
75 Patients who met the criteria were randomly assigned to deanxit group or placebo group: sertraline (75 mg/day) plus deanxit (one piece/day) (N = 38), or sertraline (75 mg/day) plus placebo (one piece/day) (N = 37) for 2 weeks, both groups received sertraline (75 mg/day) in the following 2 weeks. Changes from baseline to day 4, day 8, day 15, and day 29 in Hamilton Rating Scale for Depression (HAM-D) and Hamilton Rating Scale for Anxiety (HAM-A) total scores were the efficacy measures. Adverse events were monitored and registered systematically during the trial.
Response rates for HAM-D scores in deanxit group and placebo group were significantly different on day 8(55.26% ± 2.56% VS 24.32% ± 2.19%, p = 0.006) and day 15(78.95% ± 3.89% VS 40.54% ± 4.18%, p = 0.001), while no statistical differences were observed on day 4 and day 29. Respectively, response rates for HAM-A scores on day 4 (34.21% ± 2.21% VS 8.11% ± 1.37%, p = 0.006), day 8 (57.89% ± 3.56% VS 18.92% ± 2.68%, p = 0.001) and day 15 (78.95% ± 4.37% VS 43.24% ± 4.68%, p = 0.002), favoring the deanxit group. However, HAM-A scores were not remarkably different at the end point. The overall safety profile of both groups was favorable with no distinct differences.
The efficacy was exhibited in the deanxit group, with evidence for similar safety. The rapid onset of sertraline plus short-term deanxit indicated that it might be an inspiring strategy to manage depression and anxiety within the first two weeks in chronic somatic diseases.
Electronic supplementary material
The online version of this article (doi:10.1186/s12888-015-0449-2) contains supplementary material, which is available to authorized users.
PMCID: PMC4403889  PMID: 25879863
Sertraline; Deanxit; Depression and anxiety; Chronic somatic diseases
19.  The Effect of Adding Ready-to-Use Supplementary Food to a General Food Distribution on Child Nutritional Status and Morbidity: A Cluster-Randomized Controlled Trial 
PLoS Medicine  2012;9(9):e1001313.
Lieven Huybregts and colleagues investigate how supplementing a general food distribution with a fortified lipid-based spread during a seasonal hunger gap in Chad affects anthropometric and morbidity outcomes for children aged 6 to 36 months.
Recently, operational organizations active in child nutrition in developing countries have suggested that blanket feeding strategies be adopted to enable the prevention of child wasting. A new range of nutritional supplements is now available, with claims that they can prevent wasting in populations at risk of periodic food shortages. Evidence is lacking as to the effectiveness of such preventive interventions. This study examined the effect of a ready-to-use supplementary food (RUSF) on the prevention of wasting in 6- to 36-mo-old children within the framework of a general food distribution program.
Methods and Findings
We conducted a two-arm cluster-randomized controlled pragmatic intervention study in a sample of 1,038 children aged 6 to 36 mo in the city of Abeche, Chad. Both arms were included in a general food distribution program providing staple foods. The intervention group was given a daily 46 g of RUSF for 4 mo. Anthropometric measurements and morbidity were recorded monthly. Adding RUSF to a package of monthly household food rations for households containing a child assigned to the intervention group did not result in a reduction in cumulative incidence of wasting (incidence risk ratio: 0.86; 95% CI: 0.67, 1.11; p = 0.25). However, the intervention group had a modestly higher gain in height-for-age (+0.03 Z-score/mo; 95% CI: 0.01, 0.04; p<0.001). In addition, children in the intervention group had a significantly higher hemoglobin concentration at the end of the study than children in the control group (+3.8 g/l; 95% CI: 0.6, 7.0; p = 0.02), thereby reducing the odds of anemia (odds ratio: 0.52; 95% CI: 0.34, 0.82; p = 0.004). Adding RUSF also resulted in a significantly lower risk of self-reported diarrhea (−29.3%; 95% CI: 20.5, 37.2; p<0.001) and fever episodes (−22.5%; 95% CI: 14.0, 30.2; p<0.001). Limitations of this study include that the projected sample size was not fully attained and that significantly fewer children from the control group were present at follow-up sessions.
Providing RUSF as part of a general food distribution resulted in improvements in hemoglobin status and small improvements in linear growth, accompanied by an apparent reduction in morbidity.
Trial registration NCT01154595
Please see later in the article for the Editors' Summary.
Editors' Summary
Good nutrition during childhood is essential for health and survival. Undernourished children are more susceptible to infections and are more likely to die from common ailments such as diarrhea than well-nourished children. Globally, undernutrition contributes to about a third of deaths among children under five years old. Experts use three physical measurements to determine whether a child is undernourished. An “underweight” child has a low weight for his or her age and gender when compared to the World Health Organization Child Growth Standards, which chart the growth of a reference population. A “stunted” child has a low height for his or her age; stunting indicates chronic undernutrition. A “wasted” child has a low weight for his or her height; wasting indicates acute undernutrition and can be caused by disasters or seasonal food shortages. Recent estimates indicate that about a fifth of young children in developing countries are underweight, and one third are stunted; in south Asia and west/central Africa, more than one tenth of children are wasted, a condition that markedly increases the risk of death.
Why Was This Study Done?
In emergency situations, international organizations support affected populations by providing “general food distributions.” Recently, there have been claims that the provision of targeted nutritional supplements within a general food distribution framework effectively prevents child wasting, but there is little evidence to support these claims. In this cluster-randomized controlled trial, the researchers investigate the effect of a targeted daily dose of a “ready-to-use supplementary food” (RUSF; a lipid-based nutrient supplement) on indicators of undernutrition in 6- to 36-month-old, non-wasted children in Chad, a country beset by a severe food crisis. Political instability in this central African country has severely reduced the nutritional status of children, and annual droughts, which affect crop production, cause a “hunger gap” between June and October. In a recent survey, one fifth of children in Chad were wasted at the beginning of this hunger gap. A cluster-randomized trial randomly assigns groups of people to receive alternative interventions and compares the outcomes in the differently treated “clusters.”
What Did the Researchers Do and Find?
The researchers randomly assigned fourteen household clusters in the city of Abeche, Chad, to the trial's intervention or control arm. All the households received a general food distribution that included staple foods; eligible children in the intervention households were also given a daily RUSF ration between June and September 2010. The researchers regularly measured the children's weights and heights, recorded illnesses reported by caregivers, and measured each child's blood hemoglobin level before and after the intervention to assess their risk of anemia, an indicator of poor nutrition. The addition of RUSF to the household food rations did not significantly reduce the cumulative incidence of wasting. That is, although fewer children in the intervention group became wasted during the trial than in the control group, this difference was not statistically significant—it could have happened by chance. However, compared to the children in the control group, those in the intervention group had a significantly greater gain in height-for-age (equivalent to a difference in height gain of 0.09 cm/month), slightly higher hemoglobin levels at the end of the study, which significantly reduced their anemia risk, and a significantly lower risk of self-reported diarrhea and fever.
What Do These Findings Mean?
Although targeted RUSF provided as part of a general food distribution had no significant effect on wasting in young children in Abeche, Chad, the intervention improved their hemoglobin status and linear growth, and reduced illness among them. Why didn't targeted RUSF prevent wasting effectively in this trial? Maybe the effect of RUSF was diluted out by the effect of the general food distribution or maybe the trial was too short to see a clear effect. Most importantly, though, the trial may have been too small to see a clear effect—the researchers were unable to enroll as many children into their trial as they had planned because of political instability in Chad, and this probably limited the trial's ability to detect small differences between the control and intervention groups. Nevertheless, because these findings provide no clear evidence that adding RUSF to a household food ration effectively prevents wasting, alternative ways to prevent acute malnutrition in Chad and other vulnerable regions of the world should be investigated.
Additional Information
Please access these websites via the online version of this summary at
This study is further discussed in a PLOS Medicine Perspective by Kathryn Dewey and Mary Arimond
Action Contra la Faim–France has a web page that describes the situation in Chad
The United Nations Childrens Fund, which protects the rights of children and young people around the world, provides detailed statistics on child undernutrition; it has detailed information, including videos, about the current food crisis in Chad and the Sahel
The WHO Child Growth Standards are available (in several languages)
The United Nations provides information on ongoing world efforts to reduce hunger and child mortality
The World Food Programme is the world's largest humanitarian agency fighting hunger worldwide; its website provides detailed information about malnutrition in Chad, including a video of the current food crisis in the country
Starved for Attention is an international multimedia campaign launched in 2010 by Médecins Sans Frontiéres (MSF) and the VII Photo agency to rewrite the story of childhood malnutrition; information about MSFs work in Chad to tackle malnutrition is available
PMCID: PMC3445445  PMID: 23028263
Background: Evidence supporting the use of serotonergic medications for the treatment of alcohol dependence is available from studies where pharmacotherapy targeted specific alcoholic subtypes. We previously established with Babor's alcohol typology that Type A “lower-risk/severity” alcoholics (n=55) had better treatment response to 14 weeks of sertraline (200mg/day) than placebo, and this was not found for Type B “higher-risk/severity” alcoholics (n=45). The purpose of this study is to assess in this original study group whether treatment gains in the Type A alcoholics were maintained, or, if treatment outcomes changed for the Type B alcoholics, after discontinuing pharmacotherapy. Methods: After the end of a 3-month course of 200mg/day of sertraline, the subjects were interviewed at several time points about their alcohol drinking, if any, using the Timeline Followback method. For 90% of the original study group, mixed effects and GEE models were used to compare monthly drinking amounts over a 6-month post-treatment period to drinking amounts in the last month of treatment. Results: We found that Type A alcoholics who had been treated with sertraline, in contrast to placebo, maintained the good outcomes they had achieved during treatment for at least 6 months following pharmacotherapy. We found that Type B alcoholics who had been treated with sertraline, in contrast to placebo, continued to show no advantage for pharmacotherapy in the 6 months after completing treatment. In addition, heavy drinking in Type B alcoholics increased over the 6 months post-pharmacotherapy in those initially treated with sertraline, compared to placebo. Conclusions: These data support the importance of considering alcohol subtype when pharmacologically treating alcohol dependence.
PMCID: PMC1435448  PMID: 15252293
Alcohol Dependence; Alcohol Subtypes; Alcohol Treatment; Sertraline; Follow-up
21.  Clinical Subtypes of Premenstrual Syndrome and Responses to Sertraline Treatment 
Obstetrics and gynecology  2011;118(6):1293-1300.
To estimate response of diagnosis and symptom-based subtypes to sertraline treatment.
This was a secondary data analysis for women who were diagnosed with premenstrual syndrome (PMS) or premenstrual dysphoric disorder and treated in three National Institutes of Health-supported clinical trials (N=447). Three PMS subtypes were identified based on predominance of psychological, physical, or both symptom types. Scores for each symptom and a total premenstrual score at baseline and endpoint were calculated from daily symptom diaries. Change from baseline after three treated menstrual cycles (or endpoint if sooner) was estimated using linear regression models adjusted for baseline severity.
The PMS and premenstrual dysphoric disorder diagnoses improved similarly with sertraline relative to placebo, while symptom-based subtypes had differential responses to treatment. The mixed symptom subtype had the strongest response to sertraline relative to placebo (Daily Symptom Rating [DSR] difference 33.80, 95% CI: 17.16, 50.44, P<0.001), and the physical symptom subtype had the poorest response to sertraline (DSR difference 9.50, 95% CI: −16.29, 35.28, P=0.470). Results based on clinical improvement (50% decrease from baseline) indicated that 8.3 participants in the mixed symptom subtype, 3.9 in the psychological subtype, and 7.1 in the physical subtype are needed to observe one woman in the subtype who would achieve clinical improvement.
The PMS and premenstrual dysphoric disorder diagnoses have similar response to sertraline treatment, but symptom-based subtypes have significantly different responses to this treatment. Mixed and psychological symptom subtypes improved while the physical symptom subtype did not improve significantly. Identifying the patient’s predominant symptoms, and their severity is important for individualized treatment and possible response to a selective serotonin reuptake inhibitor.
PMCID: PMC3222869  PMID: 22105258
22.  Retrospective comparison of cognitive behavioral therapy and symptom-specific medication to treat anxiety and depression in throat cancer patients after laryngectomy 
Shanghai Archives of Psychiatry  2014;26(2):95-100.
Laryngectomy, a common treatment for laryngeal cancer, is a disabling operation that can induce tremendous stress, but little is known about how to alleviate the psychological effects of the operation.
Compare the effectiveness of cognitive behavioral therapy (CBT) and medication in treating anxiety and depression among throat cancer patients after laryngectomy.
Review of medical records of the psychological outpatient clinic in the Third People’s Hospital of Huzhou City between March 2009 and May 2013 identified 63 patients with post-laryngectomy depression or anxiety disorders who received 8 weeks of one-on-one treatment with CBT (in which patients responded in writing because they were unable to speak) and 56 patients who received 8 weeks of treatment with buspirone (n=11), sertraline (n=9) or both busipirone and sertraline (n=36). The treatment provided (CBT or medications) was based on the stated preference of the patient. The Zung Self-rating Anxiety Scale (SAS) and the Zung Self-rating Depression Scale (SDS) were administered before and after treatment.
After 8 weeks of treatment the mean SAS and SDS scores had decreased significantly in both groups and the prevalence of clinically significant anxiety and depression (based on SAS and SDS cutoff scores) had dropped dramatically. There were, however, no significant differences between the two treatment methods. In the medication group 32% of participants experienced one or more adverse reactions during treatment, but none of these were severe enough to require withdrawal from treatment.
CBT is an effective, short-term treatment for reducing the anxiety and depressive symptoms that often occur after an individual is diagnosed with cancer or treated for cancer. There is robust evidence that treatment of these psychological symptoms can improve both the quality of life and course of illness in cancer patients, so oncologists and other clinicians need to regularly screen patients with cancer and other chronic life-threatening conditions for anxiety and depression and, if present, actively promote the treatment of these symptoms. This study shows that CBT can be effective for cancer patients even when they are unable to speak.
PMCID: PMC4120290  PMID: 25092955
cognitive behavior therapy; laryngectomy; depression; anxiety disorders
23.  Sertraline versus amitriptyline in the prophylactic therapy of non-depressed chronic tension-type headache patients 
Patients with chronic tension- type headache (CTTH) are the most difficult to treat. Tricyclic antidepressants are the first-line therapeutic agents, but their anticholinergic side effects limit their usage. Selective serotonin reuptake inhibitors (SSRI) with fewer side effects than tricyclic antidepressants have also been used in treatment of CTTH, but the results are conflicting. In this study, prophylactic action of sertraline in treatment of nondepressed patients with CTTH was investigated and compared with amitriptyline in a prospective, randomized, open label, parallel-group study. A 4-week baseline period was followed by a 12-week treatment period with either 50 mg sertraline (n=41 patients) or 25 mg amitriptyline (n=44 patients). Efficacies of treatments were determined by using a headache diary, in which patients recorded the occurrence, number, intensity and duration of headaches in days, analgesic drug consumption and any adverse events. Both drugs reduced headache symptoms and analgesic drug consumption at the first, second and third months of treatment compared to baseline values. There was significant superiority of amitriptyline in the headache symptoms and drug consumption reductions versus sertraline at the second and third months of treatment. Side effects were more favorable in the sertraline-treated patients, but dropouts were similar in both groups. These results suggest that both drugs were effective in the treatment of non-depressed patients with CTTH, but in comparison between groups, amitriptyline was more effective than sertraline.
PMCID: PMC3452139
Chronic tension-type headache; Prophylaxis; Sertraline; Amitriptyline
24.  Pilot pharmacologic randomized controlled trial for psychogenic nonepileptic seizures(e–Pub ahead of print)(LOE Classification) 
Neurology  2010;75(13):1166-1173.
There have been few treatment trials for psychogenic nonepileptic seizures (PNES). Some psychotherapies have been shown to improve PNES and comorbid symptom outcomes. We evaluated a pharmacologic intervention to test the hypothesis that sertraline would reduce PNES.
We conducted a pilot, double-blind, randomized, placebo-controlled trial in an academic medical hospital with epilepsy center outpatients. Subjects aged 18 to 65 years diagnosed with video-EEG–confirmed PNES were treated with flexible-dose sertraline or placebo over 12 weeks. Seizure calendars and symptom scales were charted prospectively. Secondary outcome measures included psychiatric symptom scales and psychosocial variables.
Thirty-eight subjects enrolled, and 26 (68%) completed the trial. Thirty-three subjects with nonzero nonepileptic seizure rates at baseline were included in intent-to-treat analysis of the primary outcome. Subjects assigned to the sertraline arm experienced a 45% reduction in seizure rates from baseline to final visit (p = 0.03) vs an 8% increase in placebo (p = 0.78). Secondary outcome scales revealed no significant between-group differences in change scores from baseline to final visit, after adjustment for differences at baseline.
PNES were reduced in patients treated with a serotonin selective reuptake inhibitor, whereas those treated with placebo slightly increased. This study provides feasibility data for a larger-scale study.
Level of evidence:
This study provides Class II evidence that flexible-dose sertraline up to a maximum dose of 200 mg is associated with a nonsignificant reduction in PNES rate compared with a placebo control arm (risk ratio 0.51, 95% confidence interval 0.25–1.05, p = 0.29), adjusting for differences at baseline.
= antiepileptic drug;
= confidence interval;
= Diagnostic and Statistical Manual of Mental Disorders, 4th edition;
= epileptic seizures;
= intent to treat;
= psychogenic nonepileptic seizures;
= posttraumatic stress disorder;
= quality of life;
= randomized controlled trial;
= Rhode Island Hospital;
= risk ratio;
= serotonin selective reuptake inhibitor;
= video-EEG.
PMCID: PMC3013487  PMID: 20739647
25.  Concurrent administration of donepezil HCl and sertraline HCl in healthy volunteers: assessment of pharmacokinetic changes and safety following single and multiple oral doses 
This study evaluated the safety and pharmacokinetics (PK) of donepezil HCl and sertraline HCl when administered separately and in combination.
This was a randomized, open-label, three-period crossover study. In consecutive dosing periods separated by washout periods of ≥3 weeks, healthy volunteers received either oral donepezil HCI 5 mg once daily for 15 days, oral sertraline HCl 50 mg once daily for 5 days followed by 10 days of once-daily sertraline HCl 100 mg, or the simultaneous administration of oral donepezil HCl and sertraline HCl. Plasma donepezil and sertraline concentrations were determined by high performance liquid chromatography/mass spectrometry. Safety was evaluated by physical and laboratory evaluations and the monitoring of adverse events (AEs).
A total of 19 volunteers (16 male and three female) were enrolled. Three male subjects withdrew from the study prematurely due to AEs (one case of nausea/stomach cramps and one case of eosinophilia during combination treatment, and one upper respiratory tract infection during treatment with sertraline HCl alone). In subjects who completed all three treatment periods (n = 16), the concurrent administration of donepezil HCl and sertraline HCl did not alter the steady-state (day 15) PK parameters of donepezil HCl. A small (<12%) but statistically significant (P = 0.02) increase in donepezil Cmax was seen after single doses of sertraline HCl and donepezil HCl on day 1 but this was not thought to be clinically meaningful. No significant differences in the tmax or AUC0–24 h of donepezil were observed between the donepezil HCl only or donepezil HCl plus sertraline HCl groups on day 1. No significant changes in sertraline PK parameters were observed either on day 1 (single dose) or on day 15 (steady state) when sertraline HCl was co-administered with donepezil HCl. Generally, the concurrent administration of donepezil HCl and sertraline HCl was well tolerated, with no serious AEs reported during the study. Some digestive system AEs tended to occur more frequently during combination treatment than with either treatment alone, but there was no statistically significant increase in the incidence of any individual AE. The most common AEs during the combination therapy were nausea and diarrhoea, which were rated as mild or moderate in severity. These AEs were also reported during the administration of each drug alone.
The co-administration of once-daily oral donepezil HCl 5 mg for 15 days and once-daily oral sertraline HCl (50 mg for 5 days increased to 100 mg for 10 days) did not result in any clinically meaningful pharmacokinetic interactions, and no unexpected AEs were observed.
PMCID: PMC1884554  PMID: 15496220
acetylcholinesterase inhibitor; Alzheimer's disease; donepezil; drug–drug interaction; pharmacokinetics; sertraline

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