Comparison of the efficacy between paroxetine and sertraline augmented with aripiprazole in patients with refractory major depressive disorder

Objective

Only two-thirds of depressive patients respond to antidepressant treatment. In recent years, addition of an atypical antipsychotic drug to ongoing treatment with an antidepressant has been considered effective and well-tolerated. In the present study, we compared the efficacy between paroxetine and sertraline augmented with aripiprazole in patients with refractory major depression.

Subjects and methods

Twenty-four patients who met the DSM-IV criteria for major depressive disorder who did not at least two different classes of antidepressants were enrolled in the study. Nine were male and thirteen were female, and their ages ranged from 28 to 66 (mean ± SD = 39 ± 12) years. Patients were prescribed paroxetine (n = 11) or sertraline (n = 13) for 4 weeks. Then, those whose scores on the 17-item Hamilton Rating Scale for Depression (HAMD17) decreased below 50% received adjunctive therapy of aripiprazole for 4 weeks.

Results

Although the use of either combination treatment decreased the HAMD17 scores compared to the respective monotherapy, there was no significant difference in HAMD17 scores between the paroxetine plus aripiprazole group and sertraline plus aripiprazole group.

Conclusion

Aripiprazole augmentation therapy with paroxetine or sertraline was equally effective and tolerated in patients with refractory major depressive order.     

Effects of venlafaxine and fluoxetine on lymphocyte subsets in patients with major depressive disorder: A flow cytometric analysis

Background

Studies have yielded conflicting results concerning flow cytometric lymphocyte analyses in patients with depression. Data about the effect of antidepressants on lymphocyte subsets are also contradictory. The aim of this study was to determine effects of venlafaxine versus fluoxetine on lymphocyte subsets in depressive patients.

Methods

Sixty-nine patients diagnosed with major depressive disorder (MDD) according to DSM-IV and 36 healthy controls are included in the study. Sixty-nine patients were randomized to take fluoxetine (FLX) (n = 33) or venlafaxine (VEN) (n = 36). Serum lymphocyte subsets included CD3, CD4, CD8, CD16/56, CD19, CD45, Anti-HLA-DR which were measured by flow cytometric analyses at baseline and 6 weeks after the start of treatment. The severity of depression was evaluated with Hamilton rating scale for depression.

Results

At baseline, patients with MDD had significantly lower CD16/56 ratio and higher CD45 ratio compared to the controls. Although numerically higher in the VEN treated patients, treatment response rates between the FLX (53%) and the VEN (75%) groups were not different statistically. CD45 values decreased significantly in the VEN group at the end of the 6 week treatment period whereas no difference was observed in the FLX group. By the 6th week, treatment responders showed a significantly higher CD16/56 ratio than non-responders. Baseline severity of depression and anxiety was positively correlated with baseline CD45 ratio and negatively correlated with baseline CD16/56 ratio. We did not observe consistent changes in the absolute number of circulating B or T cells, nor in the helper/inducer (CD4) or suppressor/cytotoxic (CD8) subsets.

Conclusions

CD16/56 was lower in patients with MDD and increased in treatment responders at 6th week. CD45 ratio was higher in patients with MDD than healthy subjects; it decreased with antidepressant treatment and was positively correlated with the severity of depression. Antidepressant treatment contributes to immune regulation in patients with major depressive disorder.     

Serum brain-derived neurotrophic factor predicts responses to escitalopram in chronic posttraumatic stress disorder

Introduction

Some studies have found that antidepressants increase serum brain-derived neurotrophic factor (BDNF) levels in patients with major depression and the expression of BDNF mRNA in limbic structures of rats.

Objectives

This study addressed whether the SSRI escitalopram increases serum BDNF levels in subjects with PTSD and whether BDNF levels are associated with treatment response.

Methods

Medically healthy male subjects (N = 16) with chronic PTSD completed a 12 week open-label trial of flexible dose (5–20 mg/day) escitalopram monotherapy. BDNF levels were obtained at baseline, and at weeks 4, 8 and 12.

Results

PTSD symptoms significantly declined over the course of the 12 week escitalopram treatment. Despite a substantial improvement in PTSD symptoms, there was virtually no change in BDNF levels over time. Nevertheless, mean BDNF levels across the trial were strongly correlated with the slope of PTSD symptoms over the 12 weeks (r = 0.58, p = 0.018). Lower mean BDNF was associated with a greater decrease in PTSD symptoms over the course of the trial.

Conclusions

PTSD subjects with low BDNF levels demonstrated the largest treatment response from an agent with putative neurotrophic effects.     

Gender difference in antidepressant-related sexual dysfunction in Taiwan

Objective

Sexual dysfunction accompanied by depression may be altered by antidepressants. The effects of antidepressants on sexual dysfunction among males and females remain to be investigated.

Methods

Three groups of subjects, drug-free patients with depression (N= 125), medicated patients with depression (N= 145) and healthy volunteers (N= 255), were recruited. A Chinese version of the Changes in Sexual Functioning Questionnaire was employed to assess sexual function as the primary outcome.

Results

Drug-free depressed females and medicated depressed males had more sexual dysfunction than healthy controls. The desire for sexual behaviors among healthy females and medicated depressed females was higher than that of drug-free depressed females.

Conclusion

Depression and antidepressants may have different impacts on the sexual function of males and females.     

Serum BDNF levels before treatment predict SSRI response in depression

Objectives

The “neurotrophin hypothesis” of depression posits a role of brain-derived neurotrophic factor (BDNF) in depression, although it is unknown whether BDNF is more involved in the etiology of depression or in the mechanism of action of antidepressants. It is also unknown whether pre-treatment serum BDNF levels predict antidepressant response.

Methods

Thirty un-medicated depressed subjects were treated with escitalopram (N = 16) or sertraline (N = 14) for 8 weeks. Twenty-five of the depressed subjects completed 8 weeks of antidepressant treatment and had analyzable data. Twenty-eight healthy controls were also studied. Serum for BDNF assay was obtained at baseline in all subjects and after 8 weeks of treatment in the depressed subjects. Depression ratings were obtained at baseline and after 8 weeks of treatment in the depressed subjects.

Results

Pre-treatment BDNF levels were lower in the depressed subjects than the controls (p = 0.001) but were not significantly correlated with pre-treatment depression severity. Depression ratings improved with SSRI treatment (p < 0.001), and BDNF levels increased with treatment (p = 0.005). Changes in BDNF levels were not significantly correlated with changes in depression ratings. However, pre-treatment BDNF levels were directly correlated with antidepressant responses (p < 0.01), and “Responders” to treatment (≥ 50% improvement in depression ratings) had higher pre-treatment BDNF levels than did “Non-responders” (p < 0.05).

Conclusions

These results confirm low serum BDNF levels in un-medicated depressed subjects and confirm antidepressant-induced increases in BDNF levels, but they suggest that antidepressants do not work simply by correcting BDNF insufficiency. Rather, these findings are consistent with a permissive or facilitatory role of BDNF in the mechanism of action of antidepressants.     

Benefits of collaborative care for post-CABG depression are not related to adjustments in antidepressant pharmacotherapy

Objective

To determine whether the use and adjustment of antidepressant pharmacotherapy accounted for the beneficial effects of collaborative care treatment on the improvement of mood symptoms and health-related quality of life (HRQoL) after coronary artery bypass graft (CABG) surgery.

Methods

In a post-hoc analysis of data from the Bypassing the Blues (BtB) trial we tested the impact of antidepressant medication on changes in depression and HRQoL from the early postoperative period to 8-month follow-up. Two hundred fifty-nine depressed post-CABG patients scoring ≥ 10 on the Patient Health Questionnaire-9 were classified in four groups according to whether or not they received antidepressants at baseline and 8-months following randomization.

Results

Patients using antidepressant pharmacotherapy at baseline and follow-up tended to be younger and female (p≤0.01), but were similar in various clinical characteristics. Just 24% (63/259) of patients were on an antidepressant at baseline which increased to 36% at follow-up (94/259). Compared to other groups, patients on antidepressants at both baseline and follow-up assessment showed the smallest improvement in mood symptoms and HRQoL. While multivariate analyses confirmed that randomization to collaborative care was associated with greater improvement in mood symptoms (odds ratio [OR] = 3.1; 95%-confidence interval [CI] = 1.8–5.4, p < 0.0001) and mental HRQoL (OR = 3.6, CI = 1.4–9.3, p = 0.01), use of antidepressant medication had no differential impact on either measure (p = 0.06 and p = 0.92, respectively).

Conclusion

The beneficial effects of collaborative care for post-CABG depression were not generated by adjustments in antidepressant medication.Trial Registration: Clinicaltrials.gov Identifier: NCT00091962.(http://clinicaltrials.gov/ct2/show/NCT00091962?term=rollman+cabg&rank=1).     

A meta-analysis of the relationship between antidepressant use in pregnancy and the risk of preterm birth and low birth weight

Objectives

To examine the relationship between antidepressant use in pregnancy and low birth weight (LBW) and preterm birth (PTB).

Data Sources and Study Selection

We searched English and non-English language articles via PubMed, CINAHL and PsychINFO (from their start dates through December 1st, 2012). We used the following keywords and their combinations: antidepressant, selective serotonin reuptake inhibitor (SSRI), pregnancy, antenatal, prenatal, birthweight, birth weight, preterm, prematurity, gestational age, fetal growth restriction, intrauterine growth restriction, and small-for-gestational age. Published studies were considered eligible if they examined exposure to antidepressant medication use during pregnancy and reported data on at least one birth outcome of interest: PTB (<37 weeks gestation) or LBW (<2500 g). Of the 222 reviewed studies, 28 published studies met the selection criteria.

Data Extraction

Two authors independently extracted study characteristics from eligible studies.

Results

Using random-effects models, antidepressant use in pregnancy was significantly associated with LBW (RR: 1.44, 95% confidence interval (CI): 1.21-1.70) and PTB (RR: 1.69, 95% CI: 1.52-1.88). Studies varied widely in design, populations, control groups and methods. There was a high level of heterogeneity as measured by I2 statistics for both outcomes examined. The relationship between antidepressant exposure in pregnancy and adverse birth outcomes did not differ significantly when taking into account drug type (SSRI vs. other or mixed) or study design (prospective vs. retrospective). There was a significant association between antidepressant exposure and PTB for different types of control status used (depressed, mixed or nondepressed).

Conclusions

Antidepressant use during pregnancy significantly increases the risk for LBW and PTB.     

Associations of depression diagnosis and antidepressant treatment with mortality among young and disabled Medicare beneficiaries with COPD

Objective

Depression is prevalent in chronic obstructive pulmonary disease (COPD) patients and a risk factor for COPD exacerbation and death. The objective of this study was to determine the associations of depression diagnosis and antidepressant treatment with mortality among Social Security Disability Insurance (SSDI)-eligible (age < 65 years who had permanent physical or mental disabilities) Medicare beneficiaries with COPD.

Method

This retrospective cohort study used a 5% random sample of SSDI-eligible Medicare beneficiaries with COPD in stand-alone Part D plans during 2006–2008 (n= 17,320). COPD and depression diagnoses were assessed during 2006. Evidence of antidepressant treatment was measured in 2006–2008. All-cause mortality was measured in 2007–2008. Cox proportional hazards models were used to examine the associations of depression diagnosis with mortality and, among depressed beneficiaries, antidepressant treatment (time dependent) with mortality after controlling for covariates.

Results

More than one third (37.3%) of SSDI-eligible beneficiaries with COPD had a baseline depression diagnosis; of those, 86.8% had evidence of antidepressant treatment. Baseline depression diagnosis was an independent risk factor for 2-year mortality [hazard ratio (HR)=1.21; 99% confidence interval (CI)=1.07–1.37]. Among depressed beneficiaries, receiving antidepressant treatment was associated with significantly lower mortality (HR=0.55; 99% CI=0.44–0.68).

Conclusion

Proactive antidepressant treatment should be considered as an intervention to reduce mortality for this young and disabled Medicare population.     

Reevaluating the role of antidepressants in cancer-related depression: a systematic review and meta-analysis

Objective

Prior reviews evaluating the role of antidepressants in cancer-related depression have drawn conflicting conclusions. These reviews have also not explored differences in efficacy and tolerability between antidepressants. We conducted a meta-analysis to address these limitations.

Method

We searched Medline (1948–2013), the Cochrane Library (1800–2013), the Cumulative Index to Nursing and Allied Health Literature (1986–2013), ClinicalTrials.gov (2013) and meeting abstracts. We included randomized trials comparing antidepressants to placebo or no treatment for cancer-related depression. We used random effects to calculate standardized mean differences (SMD).

Results

Of 5178 potentially eligible citations, 9 trials (1169 subjects) met inclusion criteria. Trials of mianserin found a robust reduction in depression scores at ≥ 4 weeks of treatment (SMD: 0.60, 95% confidence interval (CI): 0.24–0.95). Similar, but less robust, results were observed with paroxetine (SMD: 0.22, 95% CI: 0.01–0.42) and fluoxetine (SMD 0.34, 95% CI: 0.02–0.66). Conversely, there was no advantage with amitriptyline or desipramine. Compared to placebo, the odds of dropping out due to side effect were higher with fluoxetine and paroxetine and lower with mianserin. Methodological quality was moderate.

Conclusions

Paroxetine, fluoxetine and mianserin improve cancer-related depression but may vary in efficacy and tolerability. High-quality, randomized trials of newer antidepressant agents are needed to identify optimal treatments for managing cancer-related depression.     

Quality of depression treatment in Black Americans with major depression and comorbid medical illness

Objective

The objective was to evaluate how comorbid type 2 diabetes (T2DM) and hypertension (HT) influence depression treatment and to assess whether these effects operate differently in a nationally representative community-based sample of Black Americans.

Methods

Data came from the National Survey of American Life (N= 3673), and analysis is limited to respondents who met lifetime criteria for major depression (MD) (N= 402). Depression care was defined according to American Psychiatric Association (APA) guidelines and included psychotherapy, pharmacotherapy and satisfaction with services. Logistic regression was used to examine the effects of T2DM and HT on quality of depression care.

Results

Only 19.2% of Black Americans with MD alone, 7.8% with comorbid T2DM and 22.3% with comorbid HT reported APA-guideline-concordant psychotherapy or antidepressant treatment. Compared to respondents with MD alone, respondents with MD+T2DM/HT were no more or less likely to receive depression care. Respondents with MD+HT+T2DM were more likely to report any guideline-concordant care (odds ratio=3.32; 95% confidence interval, 1.07–10.31).

Conclusions

Although individuals with MD and comorbid T2DM+HT were more likely to receive depression care, guideline-concordant depression care is low among Black Americans, including those with comorbid medical conditions.     

High-frequency rTMS treatment increases left prefrontal myo-inositol in young patients with treatment-resistant depression

Background

Neuroimaging studies suggest that the prefrontal cortex (PFC) is involved in the pathophysiology of major depression. Repetitive transcranial magnetic stimulation (rTMS) as an antidepressant intervention has increasingly been investigated in the last two decades. In this study metabolic changes within PFC of severely depressed patients before and after rTMS were evaluated by proton magnetic resonance spectroscopy (1H-MRS).

Method

Thirty-four young depressed patients with treatment-resistant unipolar depression were enrolled in a double-blind, randomized study〔active ((n = 19) vs. sham(n = 15)), and the PFC was investigated before and after high-frequency (15 Hz) rTMS using 3-tesla proton magnetic resonance spectroscopy. Response was defined as a 50% reduction of the Hamilton depression rating scale. The results were compared with 28 age- and gender-matched healthy controls.

Results

In depressive patients a significant reduction in myo-inositol (m-Ino) was observed pre-rTMS (p < 0.001). After successful treatment, m-Ino increased significantly in left PFC and the levels no longer differed from those of age-matched controls. In addition to a positive correlation between clinical improvement and an increment in m-Ino ratio, a correlation between clinical improvement and early age onset was observed.

Conclusions

Our results support the notion that major depressive disorder is accompanied by state-dependent metabolic alterations, especially in myo-inositol metabolism, which can be partly reversed by successful rTMS.     

Minocycline as adjunctive therapy for patients with unipolar psychotic depression: an open-label study

Background

Approximately 25% of patients admitted to a hospital as a result of depression are actually suffering from psychotic depression. Psychotic symptoms can be present in patients with either unipolar depression or bipolar depression and can be difficult to treat. It was reported the second-generation tetracycline may exert potential antidepressant effects through its robust neuroprotective activities, which include neurogenesis, antioxidation, and anti-glutamate excitotoxicity, and may direct regulation of pro-inflammatory agents.

Methods

This was a 6-week, open-label study to evaluate the efficacy and safety of minocycline in combination with antidepressants in adult inpatients (n = 25) diagnosed with major depression with psychotic features (psychotic depression) according to DSM-IV-TR. The primary endpoint was the change from baseline in the Hamilton Depression Rating Scale (HAM-D-21) score from baseline to week 6. Secondary endpoints were changes in the Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impression (CGI) Scale scores from baseline to week 6. Spontaneously reported adverse events were recorded.

Results

The patients' average age was 46.9 ± 10.2 years. Minocyline (150 mg/day) in combination with antidepressants (fulvoxamine, paroxetine, and sertraline) provided significant improvement in depression. Mean (± SD) HAM-D-21 was reduced to 6.7 ± 1.9 at week 6 from a baseline value of 40.4 ± 2.5. Significant improvement of psychotic symptoms (mean ± SD) was indicated by the decrease in BPRS scores from baseline (63.3 ± 8.7) to week 6 (4.6 ± 2.4). No serious adverse events occurred.

Conclusions

These preliminary data suggest that minocycline in combination with antidepressants is effective and well tolerated in the treatment of unipolar psychotic depression. Further studies using larger, double-blind, parallel-group design are warranted to confirm these findings.     

Successful treatment with Yokukansan for behavioral and psychological symptoms of Parkinsonian dementia

Objective

To evaluate the efficacy and safety of Yokukansan, a traditional Chinese herbal medicine, for treating behavioral and psychological symptoms of dementia (BPSD) in patients with Parkinson disease (PD; n = 7) and those with PD with dementia (PDD; n = 7).

Background

BPSD are often seen in patients with senile dementia and have serious deleterious effects on the lives of patients and caregivers. Recent studies indicate that the traditional Chinese herbal medicine Yokukansan may be safe and beneficial for the treatment of BPSD patients.

Methods

We treated 7 PD and 7 PDD patients for 4 weeks with Yokukansan and observed them without Yokukansan for 4 weeks. Changes in behavioral and psychological symptoms were evaluated every 4 weeks according to the Neuropsychiatric Inventory (NPI) scale.

Results

Significant improvements in behavioral and psychological symptoms, particularly in the incidence and duration of hallucinations, were observed in most PD and PDD patients after 4 weeks of Yokukansan treatment. No significant changes were observed in the laboratory tests, cognitive function, activities of daily living, or parkinsonism.

Conclusion

Our results suggest that Yokukansan improves BPSD in both PD and PDD patients without worsening their cognitive function, ability to perform activities of daily living, or parkinsonism.     

Is switching antidepressants following early nonresponse more beneficial in acute-phase treatment of depression?: a randomized open-label trial

Rationale

Treatment guidelines for major depressive disorder (MDD) recommend a continuous use of antidepressants for several weeks, while recent meta-analyses indicate that antidepressant efficacy starts to appear within 2 weeks and early treatment nonresponse is a predictor of subsequent nonresponse.

Objectives

We prospectively compared 8-week outcomes between switching antidepressants and maintaining the same antidepressant in early nonresponders, to generate a hypothesis on possible benefits of early switching strategy.

Method

Patients with MDD without any treatment history for the current episode were included. When subjects failed to show an early response (i.e., ≥ 20% improvement in the Montgomery-Åsberg Depression Rating Scale (MADRS)) to the initial treatment with sertraline 50 mg at week 2, they were randomly divided into two groups; in the Continuing group, sertraline was titrated at 50-100 mg, whereas sertraline was switched to paroxetine 20-40 mg in the Switching group. A primary outcome measure was a response rate (i.e., ≥ 50% improvement in the MADRS) at week 8.

Results

Among 132 subjects, 41 subjects showed early nonresponse. The Switching group (n = 20) showed a higher rate of responders than the Continuing group (n = 21) (75% vs. 19%: p = 0.002). Further, the Switching group was also superior in the rate of remitters (total score of ≤ 10 in the MADRS) (60% vs. 14%: p = 0.004) and continuous changes in the MADRS (19.0 vs. 7.5: p < 0.001).

Conclusions

Our preliminary findings suggest that patients with MDD who fail to show early response to an initial antidepressant may derive benefits from the early switching antidepressants in the acute-phase treatment of depression.     

Is cognitive behaviour therapy of benefit for melancholic depression?

Objective

This paper seeks to determine the relevance and likely salience of cognitive behaviour therapy (CBT) as a treatment for melancholic depression.

Methods

The findings of a randomised trial comparing 12-week outcome of 18 patients with melancholic depression receiving antidepressant medication and 11 receiving CBT were evaluated, and qualitative explanations for the outcomes were provided principally by the treating CBT practitioners.

Results

In the trial, CBT showed no improvement in depression severity in the first four weeks and then some level of improvement over the subsequent eight weeks. Outcome was superior for those receiving antidepressant medication at 12 weeks and was first demonstrated at four weeks. The benefits of CBT appeared to be in settling anxiety, dealing with cognitive processing of having a melancholic depression and addressing any personality vulnerabilities.

Conclusion

While a pilot study, our qualitative reports indicate that CBT may provide a useful role in managing melancholia as an adjunct to antidepressant medication. Future studies examining such a combination treatment model should seek to determine if indicative data provided here argue for a sequencing model of CBT being introduced after medication has addressed core biological underpinnings.     

Prevalence of depressive symptoms and predictors of treatment among U.S. adults from 2005 to 2010

Objectives

To determine nationally representative estimates of the prevalence of depressive symptoms and factors associated with treatment among those with moderate to severe symptoms.

Methods

A cross-sectional, retrospective analysis of adults age ≥ 18 years in the 2005–2010 National Health and Nutrition Examination Survey data who responded to the Patient Health Questionnaire (PHQ-9) was conducted (n= 13,320). Depressive symptoms and severity were defined by PHQ-9 scores. Depression treatment was defined as either receiving antidepressants or seeing a mental health professional. Multivariable logistic regression analyses using population weights identified factors associated with having depressive symptoms and receipt of any treatment.

Results

The prevalence of depressive symptoms increased from 20.92% to 25.66% over 6 years. Among patients with moderate to severe depression, 38.66% received treatment. Multivariable analyses found that being female, other Hispanic, younger age, having certain chronic comorbidities or previous hospitalization, no health insurance and in poverty status were associated with having depressive symptoms (P< .05). Among patients with moderate to severe depression, being female, white, younger age, having comorbidities (arthritis and hypertension) or previous hospitalization were associated with receipt of treatment (P< .05).

Conclusions

The prevalence of depressive symptoms is high, and only a small portion of patients with moderate to severe depression received treatments. Treatment disparities exist and need improvement.     

The influence of patients' preference/attitude towards psychotherapy and antidepressant medication on the treatment of major depressive disorder

Background and objectives

Preferences and attitudes patients hold towards treatment are important, as these can influence treatment outcome. In depression research, the influence of patients' preference/attitudes on outcome and dropout has mainly been studied for antidepressant medication, and less for psychological treatments. We investigated the effects of patients' preference and attitudes towards psychological treatment and antidepressant medication on treatment outcome and dropout, and tested specificity of effects.

Methods

Data are based on a randomized trial testing the effectiveness of behavioural activation (BA) vs antidepressant medication (ADM) for major depression (MDD) in Iran. Patients with MDD (N = 100) were randomized to BA (N = 50) or ADM (N = 50). Patients' preference/attitudes towards psychotherapy and ADM were assessed at baseline and associated with dropout and treatment outcome using logistic regression and multilevel analysis.

Results

High scores on psychotherapy preference/attitude and low scores on ADM preference/attitude predicted dropout from ADM, while no association between dropout and preference/attitude was found in BA. Psychotherapy preference/attitude moderated the differential effect of BA and ADM on one outcome measure, but the association disappeared after one year.

Limitations

Because in Iran most patients have only access to ADM, offering a psychological treatment for depression could attract especially those patients that prefer this newly available treatment.

Conclusions

Patients' preferences and attitudes towards depression treatments influence dropout from ADM, and moderate the short-term difference in effectiveness between BA and ADM. The fact that dropout from BA was not affected by preference/attitude speaks for its acceptability among patients.     

Interaction of serotonin-related genes affects short-term antidepressant response in major depressive disorder

Background

Four serotonin-related genes including guanine nucleotide binding protein beta polypeptide 3 (GNB3), 5-hydroxytryptamine receptor 1A (HTR1A; serotonin receptor 1A), 5-hydroxytryptamine receptor 2A (HTR2A; serotonin receptor 2A), and solute carrier family 6 member 4 (SLC6A4; serotonin neurotransmitter transporter) have been suggested to be candidate genes for influencing antidepressant treatment outcome. The aim of this study was to explore whether interaction among these genes could contribute to the pharmacogenomics of short-term antidepressant response in a Taiwanese population with major depressive disorder (MDD).

Methods

Included in this study were 101 MDD patients who were treated with antidepressants, 35 of whom were rapid responders and 66 non-responders after 2 weeks of treatment. We genotyped four single nucleotide polymorphisms (SNPs), including GNB3 rs5443 (C825T), HTR1A rs6295 (C-1019G), HTR2A rs6311 (T102C), and SLC6A4 rs25533, and employed the generalized multifactor dimensionality reduction (GMDR) method to investigate gene–gene interactions.

Results

Single-locus analyses showed the GNB3 rs5443 polymorphism to be associated with short-term antidepressant treatment outcome (P-value = 0.029). We did not correct for multiple testing in these multiple exploratory analyses. Finally, the GMDR approach identified a significant gene–gene interaction (P-value = 0.025) involving GNB3 and HTR2A, as well as a significant 3-locus model (P-value = 0.015) among GNB3, HTR2A, and SLC6A4.

Conclusions

These results support the hypothesis that GNB3, HTR2A, and SLC6A4 may play a role in the outcome of short-term antidepressant treatment for MDD in an interactive manner. Future research with independent replication using large sample sizes is needed to confirm the functions of the candidate genes identified in this study as being involved in short-term antidepressant treatment response.     

Relationship between inflammation and metabolic syndrome following treatment with paliperidone for schizophrenia

Objective

Metabolic syndrome and antipsychotic medications are associated with inflammation. This study investigated the relationship between inflammation and metabolic syndrome in patients with schizophrenia. It also examined the effects of paliperidone extended release (ER) treatment on metabolic parameters.

Methods

Data were analyzed from schizophrenic patients who participated in a multi-center, open-label, non-comparative clinical trial. Anthropomorphic measurements (i.e., weight, waist circumference, and blood pressure) were assessed along with fasting laboratory values, including white blood cell (WBC) count, glucose, high-density lipoprotein, and triglycerides.

Results

Among the 225 patients at baseline, the group with the highest WBC count displayed a 5.9-fold risk for metabolic syndrome compared with that of the lowest group. An increase of 10³ WBCs/μL was associated with a 1.4-fold increased risk for metabolic syndrome. After 24 weeks of treatment with paliperidone ER, significant increases were observed in waist circumference and body weight. Changes in WBC count were positively correlated with changes in waist circumference.

Conclusions

Schizophrenic patients with high levels of inflammation should be carefully monitored for metabolic syndrome. Moreover, strategies to reduce inflammation and obesity may prevent metabolic syndrome in patients with schizophrenia who take atypical antipsychotic medication.     

A randomized double-blind clinical trial on analgesic efficacy of fluoxetine for persistent somatoform pain disorder

Objectives

To verify the efficacy and safety of fluoxetine in treating patients with persistent somatoform pain disorder (PSPD).

Methods

In this 8-week, randomized double-blind placebo-controlled study, 80 patients with an ICD-10 diagnosis of PSPD were randomly assigned to receive 20 mg fluoxetine or a placebo. Several psychological scales including Medical Outcomes Study Pain Measures (MOSPM), Hamilton Depression Scale-17 items (HAMD₁₇) and Treatment Emergent Symptom Scale (TESS) were used to assess analgesic efficacy and safety of fluoxetine, and the possible analgesic mechanism of fluoxetine was preliminarily analyzed. All data were analyzed by SPSS11.5 with t-test, one-way ANOVA and a mixed-effects model repeated measures analysis. Intent-to-treat (ITT) analysis was performed and the last observation carry forward (LOCF) was used for missing values.

Results

There was a significant difference of MOSPM total score between the fluoxetine and placebo group after 2 weeks of treatment. The analgesic effect of fluoxetine was related with treatment time, and depressive patients showed a better analgesic effect than non-depressive patients. An adverse effect of fluoxetine was scarcely found.

Conclusions

Fluoxetine has a better analgesic effect than a placebo in treating persistent somatoform pain disorder, and is considered a safe treatment; its analgesic effect may be related to an antidepressant effect.