Age of onset and corpus callosal morphology in major depression

Background

The corpus callosum and related white matter projections have been implicated in major depressive disorder (MDD). Previously, we found a smaller genu in adolescents with MDD as compared to controls. To date, no study has examined the age of depression onset (adult vs. pediatric) as it relates to genu area in adults with MDD.

Methods

The area of the corpus callosum and its sub-regions were measured in 21 MDD subjects with pediatric age of onset (≤18 years) (29.48±7.62 years; 16 female, 5 male) and 31 MDD subjects with adult age of onset (≥19 years) (41.42±8.85; 17 female, 14 male) and 19 healthy controls (32.89±years 9.98; 11 female, 8 male) using magnetic resonance imaging (MRI).

Results

A difference in genu area was noted between groups (p=0.03), after co varying for age with post-hoc tests revealing that the difference was driven by the subjects with an MDD onset of pediatric age (p=0.035). No other sub-regions or total corpus callosum area demonstrated a significant difference. Genu area correlated with age in controls (p=0.02) but not in MDD patients (p=0.35). No significant correlation was found between the confound illness duration and genu area in MDD subjects with pediatric age of onset.

Limitations

Confirmation and extension of our findings requires a larger sample size and usage of diffusion tensor imaging.

Conclusions

Our findings provide additional evidence of abnormalities in the genu of the corpus callosum in early onset depression that persist into adulthood.     

Psychological insulin resistance in geriatric patients with diabetes mellitus

Objective

To determine the extent to which geriatric patients with diabetes mellitus experience psychological insulin resistance (PIR).

Methods

A total of 67 unselected geriatric patients with diabetes (mean age 82.8 ± 6.7 years, diabetes duration 12.2 [0.04–47.2] years, 70.1% female) were recruited in a geriatric care center of a university hospital.A comprehensive geriatric assessment (CGA) was performed including WHO-5, Hospital Anxiety and Depression Scale (HADS), Mini Mental State Examination (MMSE) and Barthel-Index. We assessed PIR using the Barriers of Insulin Treatment Questionnaire (BIT) and the Insulin Treatment Appraisal Scale in a face-to-face interview.

Results

Insulin-naïve patients (INP) showed higher PIR scores than patients already on insulin therapy (BIT-sum score: 4.3 ± 1.4 vs. 3.2 ± 1.0; p < 0.001). INP reported in the BIT increased fear of injection and self-testing (2.4 ± 2.4 vs. 1.3 ± 0.8; p = 0.016), expect disadvantages from insulin treatment (2.7 ± 1.6 vs. 1.9 ± 1.4; p = 0.04), and fear of stigmatization by insulin injection (5.2 ± 2.3 vs. 3.6 ± 2.6; p = 0.008). Fear of hypoglycemia, however, did not differ significantly (6.3 ± 2.8 vs. 5.1 ± 3.1; p = 0.11). Depression was not shown to be a barrier to insulin therapy.

Conclusion

INP with diabetes have a significantly more negative attitude toward insulin therapy in comparison to patients already on insulin.

Practice implications

Systematic assessment of barriers of insulin therapy, individualized diabetes treatment plans and information of patients may help to overcome such negative attitudes, leading to quicker initiation of therapy, improved adherence to treatment and a better quality of life.     

Predicting relapse in major depressive disorder using patient-reported outcomes of depressive symptom severity,functioning, and quality of life in the individual burden of illness index for depression (IBI-D)

Background

Patients with Major Depressive Disorder (MDD) often experience unexpected relapses, despite achieving remission. This study examines the utility of a single multidimensional measure that captures variance in patient-reported Depressive Symptom Severity, Functioning, and Quality of Life (QOL), in predicting MDD relapse.

Methods

Complete data from remitted patients at the completion of 12 weeks of citalopram in the STAR*D study were used to calculate the Individual Burden of Illness index for Depression (IBI-D), and predict subsequent relapse at six (n=956), nine (n=778), and twelve months (n=479) using generalized linear models.

Results

Depressive Symptom Severity, Functioning, and QOL were all predictors of subsequent relapse. Using Akaike information criteria (AIC), the IBI-D provided a good model for relapse even when Depressive Symptom Severity, Functioning, and QOL were combined in a single model. Specifically, an increase of one in the IBI-D increased the odds ratio of relapse by 2.5 at 6 months (β=0.921±0.194, z=4.76, p<2×10⁻⁶), by 2.84 at 9 months (β=1.045±0.22, z=4.74, p<2.2×10⁻⁶), and by 4.1 at 12 months (β=1.41±0.29, z=4.79, p<1.7×10⁻⁶).

Limitations

Self-report poses a risk to measurement precision. Using highly valid and reliable measures could mitigate this risk. The IBI-D requires time and effort for filling out the scales and index calculation. Technological solutions could help ease these burdens. The sample suffered from attrition. Separate analysis of dropouts would be helpful.

Conclusions

Incorporating patient-reported outcomes of Functioning and QOL in addition to Depressive Symptom Severity in the IBI-D is useful in assessing the full burden of illness and in adequately predicting relapse, in MDD.     

Impact of self-reported juvenile abuse on treatment outcome in patients with major depressive disorder

Background

We assessed the impact of juvenile abuse (emotional, physical, or sexual) on response to treatment in adults with major depressive disorder (MDD) suboptimally responsive to antidepressant therapy.

Methods

A post hoc analysis explored the relationship between self-reported history of juvenile abuse and response to risperidone or placebo augmentation during a 6-week double-blind study period in patients with MDD suboptimally responsive to a previous adequate trial of antidepressant monotherapy.

Results

Overall, only one clinical measure showed a small, but statistically significant difference in outcome between patients with abuse versus without abuse (HRSD-17). In patients reporting abuse (n=141), improvement with risperidone versus placebo augmentation was greater on several measures: HRSD-17 total and 2 subscale scores, responder rates, Q-LES-Q, and PaRTS-D. In patients without abuse (n=127), only two measures showed significant improvement: HRSD-17 subscale and PaRTS-D. Responder rates (HRSD-17) were: 40.9% (risperidone) versus 23.1% (placebo; p=0.01; odds ratio=2.7) in those with abuse, and 41.0% versus 34.4% (p=0.39; odds ratio=1.4) in those without. Adverse events rates were: 37.0% (risperidone) and 54.4% (placebo) in patients with abuse, and 56.3% and 55.6% in those without.

Limitations

Analysis not preplanned. Validated questionnaire not used to determine abuse status.

Conclusions

Self-reported juvenile abuse history may impact response to risperidone augmentation therapy in adults with MDD suboptimally responsive to antidepressants. Abuse status may reduce placebo response and reporting of adverse events.     

Association of genetic variation in CACNA1C with bipolar disorder in Han Chinese

Background

A growing body of evidence highlights the existence of shared genetic susceptibility to both major depressive disorder (MDD) and bipolar disorder (BD), suggesting some potential genetic overlap between the disorders. Genome-wide association studies have identified consistent association of single nucleotide polymorphisms of the α-1 C subunit of the L-type voltage-gated calcium channel gene (CACNA1C) with MDD and BD, suggesting CACNA1C as a promising candidate gene for susceptibility to mood disorders. In the present study, we tested the association of CACNA1C with MDD and BD in Han Chinese.

Methods

We genotyped three potentially functional polymorphisms in 635 MDD patients, 286 BD patients and 730 normal, control patients.

Results

The genotype frequencies of SNP rs1051375 showed statistically significant differences between the BD and control groups (P=0.005). At the allele level, the difference of G allele frequency of rs1051375 between BD patients and control subjects was also significant (P=0.011; OR=1.30, 95% CI: 1.06–1.58). We found that GG genotype of rs1051375 carriers had a lower age at onset than those with the AG or AA genotype, and the mean±standard deviation ages at onset of GG, AG and AA carriers were 24.04±4.22, 25.76±4.75 and 25.78±4.33 years, respectively. Neither genotype nor allele frequencies of the three polymorphisms were found to be significantly different between the MDD patients and control subjects.

Limitations

The relative small sample size in BD group should be considered a limitation of this study.

Conclusions

Our initial findings support a potential association of CACNA1C as a genetic risk factor for BD susceptibility.     

Risk of developing diabetes mellitus and hyperlipidemia among patients with bipolar disorder,major depressive disorder,and schizophrenia: A 10-year nationwide population-based prospective cohort study

Background

The high comorbidity of metabolic side effects with severe mental disorders (SMDs), including bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia, had gained much attention, because the excess mortality of these patients is mainly due to physical illness. However, most of these studies were with cross-sectional study design, the time course of metabolic side effects and SMD cannot be elucidated without a cohort study.

Method

Using a nationwide database with a large sample size and a matched control cohort study design, we enrolled patients with SMDs but without diagnoses of and medications for DM and hyperlipidemia from 1996 to 2000, and followed them to the end of 2010. We compared them with age and gender-matched controls (1:4) for the incidence of DM and hyperlipidemia.

Results

The identified cases were 367 patients with BD, 417 patients with MDD, and 1993 patients with schizophrenia, with average age of 45.3±14.0, 46.5±13.7, and 45.9±12.3, respectively. The patients with BD and schizophrenia had increased risk of initiation of anti-diabetic medications (10.1% vs. 6.3%, p=0.012; 13.3% vs. 7.2% p<0.001; respectively), and anti-hyperlipidemia medications (15.8% vs.10.5%, p=0.004; 14.2% vs.12.1%, p=0.005; respectively) than the controls. After controlling age, gender, urbanization, and income, the Cox regression model showed significantly increased risk of initiation of anti-diabetic medications among patients with BD (hazard ratio (HR) of 1.702, 95% confidence interval (CI): 1.155–2.507) and schizophrenia (HR of1.793, 95% CI: 1.532–2.098). Increased risk of initiation of anti-hyperlipidemia medications was also noted among patients with BD (HR of 1.506, 95% CI: 1.107–2.047) and schizophrenia (HR of 1.154, 95% CI: 1.002–1.329). The patients with MDD did not show increased risk of initiation of these medications than the controls.

Conclusions

This first 10-year nationwide population-based prospective matched control cohort study showed increased risks of initiation of anti-diabetic and anti-hyperlipidemia medications among patients with BD and schizophrenia. No significant increased risk was noted among the patients with MDD.     

rTMS for pharmacoresistant major depression in the clinical setting of a psychiatric hospital: Effectiveness and effects of age

Background

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive method of brain stimulation used in the treatment of drug-resistant major depressive disorder (MDD). It has been suggested that the efficacy of rTMS decreases with the age of the patient, but the data are contradictory. Here, we analyze in our clinical setting the efficacy of a 3-week rTMS treatment in drug-resistant MDD during a 3 month period and the potential influence of age on this efficacy.

Methods

Stimulation consisted of 15 sessions of rTMS over the dorsolateral prefrontal cortex. Clinical evaluations included the Hamilton Depression Rating Scale (HDRS), and the Beck Depression Inventory (BDI) at baseline, after 3 weeks of treatment, and 1 month and 3 months after the last session.

Results

Data from 93 patients issued from the 178 patients active file were analyzed. The antidepressant effect observed in the two age groups (<65 and ≥65) did not differ at the end of the treatment and 3 months later, with a comparable number of responders (50% decrease in HDRS score from baseline) (53.3% for age <65 versus 46.7% for age ≥65, p=0.51). The treatment had a significant effect over time. We found no evidence of the age affecting outcome at 3 months after the last session.

Limitations

Previous antidepressant treatments, and therapeutic drug use modifications after rTMS treatment, degree of pharmaco-resistance or duration of current episode are not reported.

Conclusion

RTMS of the DFPLC is effective as an add-on treatment for cases of pharmacologically refractory major depression, independent of the patient age.     

Evaluation of a treatment and teaching refresher programme for the optimization of intensified insulin therapy in type 1 diabetes

Objective

Evaluation of an ambulatory diabetes teaching and treatment refresher programme (DTTP) for the optimization of intensified insulin therapy in patients with type 1 diabetes (refresher course).

Methods

85 outpatients took part in this prospective multicentre trial. Metabolic and psychosocial data were analyzed at baseline (V1), 6 weeks (V2) and 12 months after DTTP (V3).

Results

In patients with baseline HbA1c > 7% (88%), HbA1c decreased by 0.36% (p = 0.004). The percentage of patients with HbA1c ≤ 7% increased from 21.3 to 34.9% and with HbA1c above 10% decreased from 6.6 to 1.6% at V3. The incidence of hypoglycaemia decreased significantly: non severe hypoglycaemia from 3.31 to 1.39 episodes/pat/week (p = 0.001) and severe hypoglycaemia from 0.16 to 0.03 episodes/pat/year (p = 0.02). The treatment satisfaction increased by +10 of maximal ±18 points. The negative influence of diabetes on quality of life decreased from −1.93 to −1.69 points (p = 0.031).

Conclusion

In a group of patients with moderately controlled diabetes type 1 who were already treated with intensified insulin therapy, metabolic control, treatment satisfaction and quality of life were improved after participation in an ambulatory DTTP without increasing insulin dosage, number of injections or insulin species.

Practice implications

This DTTP is effective for the optimization of intensified insulin therapy.     

The relationship between positive and negative automatic thought and activity in the prefrontal and temporal cortices: A multi-channel near-infrared spectroscopy (NIRS) study

Background

Recently, neurobiological studies of the cognitive model of depression have become vastly more important, and a growing number of such studies are being reported. However, the relationship between the proportion of positive and negative automatic thought and activity in the prefrontal and temporal cortices has not yet been explored. We examined the relationship between brain activity and the proportion of positive and negative automatic thought in patients with major depressive disorder (MDD), using multi-channel near-infrared spectroscopy (NIRS).

Methods

We recruited 75 individuals with MDD (36 females; mean age=39.23±12.49). They completed the Hamilton Rating Scale for Depression, Automatic Thoughts Questionnaire-Revised, Japanese version of the National Adult Reading Test, and the State-Trait Anxiety Inventory. Brain activation was measured by 52-channel NIRS.

Results

We found that activation in the vicinity of the right superior temporal gyrus is related to a deviation to negative of the proportion of positive and negative thoughts in individuals with MDD. Left dorsolateral prefrontal cortex activity was higher in the group with comparatively frequent positive thought.

Limitations

Our participants were patients taking antidepressant medication, which is known to influence brain activity. Second, the poor spatial resolution of NIRS increases the difficulty of identifying the measurement position.

Conclusions

We found that activation of the prefrontal and temporal cortices is related to the proportion of automatic thoughts in the cognitive model of depression.     

Neural response to emotional stimuli associated with successful antidepressant treatment and behavioral activation

Background

Major Depressive Disorder (MDD) is a leading cause of disability globally. Currently available treatments have limited efficacy and combination strategies are frequently used. Several lines of research have demonstrated that MDD patients experience impairments in various components of affective processing, including regulation of affective states.

Aim

To identify baseline and 1-week neuroimaging predictors of response to a 6-week trial of fluoxetine/olanzapine combination treatment during an affective processing task.

Methods

Twenty-one MDD patients and 18 healthy controls were enrolled in the study. MDD patients were treated for 6 weeks with fluoxetine (40–60 mg/day) and olanzapine (5–12.5 mg/day). All participants viewed images from the International Affective Picture Rating System during a functional magnetic resonance (fMRI) scan at baseline and 1 week.

Results

There was a 57% response rate (defined as a 50% decrease in Hamilton Rating Scale for Depression-17 item) at 6 weeks. At baseline, responders had increased premotor activity while viewing negative images compared to non-responders and healthy controls. Higher baseline premotor activity was also predictive of greater percent change on the HAMD-17 and improvement in negative disposition and behavioral drive. Non-responders exhibited increased insular activity at baseline compared to responders. Higher activity in the posterior cingulate cortex was also predictive of greater percent change on the HAMD-17. Change from baseline to 1 week did not produce any significant predictive findings.

Conclusions

Treatment with fluoxetine/olanzapine demonstrated similar biomarkers of response to monotherapeutic strategies. In particular, posterior cingulate cortex, anterior insula, and premotor cortex may show predictive differences in their response to affective images prior to treatment. Further research needs to be conducted to determine the utility of early changes in emotion circuitry in predicting antidepressant response.     

Associations between depression severity and purinergic receptor P2RX7 gene polymorphisms

Background

Major depressive disorder (MDD) and bipolar disorder (BPD) have significant genetic predisposition. The P2RX7 gene (coding for P2X7 purinergic receptor) has been suggested as a susceptibility gene for both MDD and BPD. In the current study the genetic effects of rs2230912 (Gln460Arg) and rs1653625 (located in the 3′ untranslated region of the P2RX7 gene) were explored in mood disorders.

Methods

Genotype frequencies were established in 315 patients (195 with MDD and 120 with BPD diagnosis) and in 373 controls. Depression severity was assessed by the clinician-rated Montgomery–Åsberg Depression Rating Scale (MADRS) and by the self-report Hospital Anxiety and Depression Scale (HADS).

Results

In the case-control analysis we did not find any significant differences between genotype frequencies of either BPD or MDD cases and controls. However, BPD patients carrying at least one rs2230912 G-allele scored higher on both MADRS and HADS-depression scale (nominal p-value was 0.028 and 0.003, respectively). The rs1653625 AA genotype was also associated with higher depression scores in the BPD group (nominal p-value of MADRS: 0.019, HADS-depression: 0.017). After correction for multiple testing, the association between rs2230912 and HADS-depression score remained significant in the BPD group (p<0.006); this genetic effect explained 9% of the variance (partial η²=0.09). In the MDD group we did not find any significant genetic effect.

Limitations

The relatively small number of BPD patients warrants for a replication study.

Conclusions

Our genetic association study supports the association between P2RX7 gene and severity of depressive symptoms in BPD patients.     

Neurocognitive changes in depressed patients in psychodynamic psychotherapy,therapy with fluoxetine and combination therapy

Background

Randomized controlled trials (RCTs) examining the efficacy of different forms of therapy for depression are relatively common. However, there are not many RCTs comparing neurocognitive effects of these treatments. Neurocognitive changes across three types of treatment for depression were compared. Long-term psychodynamic psychotherapy (LTPP) was compared with fluoxetine treatment, and their combination, in the treatment of moderate depression.

Methods

A 272 adult patients with beck depression inventory (BDI) scores 20–35 were randomized to receive LTPP, fluoxetine monotherapy or their combination for a 24 months period. The Wechsler adult intelligence scale version III (WAIS-III) was the primary neuropsychological measure.

Result

Multilevel mixed model analyses indicated that there were neurocognitive changes within and between treatments, with statistically significant differences over time (p>.01). LTPP and combined treatment seemed to be more efficacious in modifying specific areas of cognition than fluoxetine alone.

Limitations

Sample very homogenous, threatening external validity.

Conclusions

LTPP and its combination with fluoxetine demonstrated to be effective for specific neurocognitive increasing in patients with moderate depression. This study suggests marked differences over time in the neurocognitive effects between the three treatment forms compared. Results found here may be of clinical relevance for building bridges between pharmacotherapy and psychodynamic psychotherapy.     

A randomized double-blind comparison of fluoxetine augmentation by high and low dosage folic acid in patients with depressive episodes

Background

Though encouraging evidence exists for the use of folic acid as an augmenting agent to antidepressants, evidence regarding its optimal dosage is lacking.

Methods

Forty-two female out-patients with moderate (with or without somatic syndrome) or severe depressive episodes (without psychotic symptoms) diagnosed as per ICD-10 criteria, were randomized in a double-blind fashion to receive either 20 mg fluoxetine and a relatively low dose folic acid (1.5 mg/day; n=23; Group I) or 20 mg fluoxetine and high dose folic acid (5 mg/day; n=19; Group II). Primary outcome measures were weekly changes of scores on Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory (BDI) for 6 weeks.

Results

Group II patients showed greater improvement in both HDRS [Mean (SD) baseline HDRS score=21 (2.3) for group I and 20.0 (1.4) for group-II; time X group interaction effect: p=0.01] and BDI [Mean (SD) baseline BDI score=25.1 (5.2) for group-1 and 23.1 (2.7) for group-II; time X group interaction effect: p=0.01]. With regard to HDRS, 7 (36.8%) group II patients remitted compared to 2 (8.7%) group I patients (p=0.03); 9 (47.4%) patients of group II responded when compared to 6 (26.1%) from group I (p=0.15). When BDI was considered, 5 (26.3%) group II patients remitted when compared to 2 (8.7%) from group I (p=0.13); 10 patients (52.6%) from group II responded when compared to 5 (21.7%) from group I (p=0.04). No adverse effects were noted in either group.

Limitations

Lack of a placebo arm and small sample size.

Conclusion

Compared to folic acid 1.5 mg/day, augmentation with 5 mg/day may be more beneficial in female patients with depressive episodes taking fluoxetine 20 mg/day.     

Evaluation of a novel educational strategy,including inhaler-based reminder labels,to improve asthma inhaler technique

Objective

To evaluate the feasibility, acceptability and effectiveness of a brief intervention about inhaler technique, delivered by community pharmacists to asthma patients.

Methods

Thirty-one pharmacists received brief workshop education (Active: n = 16, Control: n = 15). Active Group pharmacists were trained to assess and teach dry powder inhaler technique, using patient-centered educational tools including novel Inhaler Technique Labels. Interventions were delivered to patients at four visits over 6 months.

Results

At baseline, patients (Active: 53, Control: 44) demonstrated poor inhaler technique (mean ± S.D. score out of 9, 5.7 ± 1.6). At 6 months, improvement in inhaler technique score was significantly greater in Active cf. Control patients (2.8 ± 1.6 cf. 0.9 ± 1.4, p < 0.001), and asthma severity was significantly improved (p = 0.015). Qualitative responses from patients and pharmacists indicated a high level of satisfaction with the intervention and educational tools, both for their effectiveness and for their impact on the patient–pharmacist relationship.

Conclusion

A simple feasible intervention in community pharmacies, incorporating daily reminders via Inhaler Technique Labels on inhalers, can lead to improvement in inhaler technique and asthma outcomes.

Practice implications

Brief training modules and simple educational tools, such as Inhaler Technique Labels, can provide a low-cost and sustainable way of changing patient behavior in asthma, using community pharmacists as educators.     

Improvements in white matter micro-structural integrity of right uncinate fasciculus and left fronto-occipital fasciculus of remitted first-episode medication-naïve panic disorder patients

Objective:

We designed this study to investigate neural correlates of white matter micro-structural integrity of remitted patients with first-episode, medication-naïve and very late-onset panic disorder

Method:

Twenty-one remitted patients with panic disorder completed treatment course with treatment of escitalopram (dose range around 10–15 mg/d). Twenty-one healthy controls were also enrolled into this study. Patients and controls all received 3-Tesla magnetic resonance imaging diffusion tensor imaging scanning at baseline and 6th week. We utilized FDT (FMRIB's Diffusion Toolbox v2.0) function of FSL (FMRIB Software Library) to calculate fractional anisotropy (FA). We compared FA values of patients and controls at baseline and 6th week to estimate the changes of FA of remitted patient group and inter-scan bias of controls. FA outputs of remitted patients and controls were compared by independent t test.

Results:

We found increased FA in some regions of right uncinate fasciculus and left fronoto-occipital fasciculus after remission in patient group (corrected p<0.05). Reduced FA of other regions of right uncinate fasciculus was still observed in remitted patients when they were compared to the control group.

Conclusion:

Subtle changes of white matter micro-structural integrity after remission might represent neural correlates of treatment effects for first-episode, medication-naïve and very late-onset panic disorder.     

Physicians’ reactions to uncertainty in the context of shared decision making

Objective

Physicians’ reactions towards uncertainty may influence their willingness to engage in shared decision making (SDM). This study aimed to identify variables associated with physician's anxiety from uncertainty and reluctance to disclose uncertainty to patients.

Methods

We conducted a cross-sectional secondary analysis of longitudinal data of an implementation study of SDM among primary care professionals (n = 122). Outcomes were anxiety from uncertainty and reluctance to disclose uncertainty to patients. Hypothesized factors that would be associated with outcomes included attitude, social norm, perceived behavioral control, intention to implement SDM in practice, and socio-demographics. Stepwise linear regression was used to identify predictors of anxiety from uncertainty and reluctance to disclose uncertainty to patients.

Results

In multivariate analyses, anxiety from uncertainty was influenced by female gender (β = 0.483; p = 0.0039), residency status (1st year: β = 0.600; p = 0.001; 2nd year: β = 0.972; p < 0.001), and number of hours worked per week (β = −0.012; p = 0.048). Reluctance to disclose uncertainty to patients was influenced by having more years in formal education (β = −1.996; p = 0.012).

Conclusion

Variables associated with anxiety from uncertainty differ from those associated with reluctance to disclose uncertainty to patients.

Practice implications

Given the importance of communicating uncertainty during SDM, measuring physicians’ reactions to uncertainty is essential in SDM implementation studies.     

New psycho-pedagogic approach to obesity treatment: A 5-year follow-up

Objective

The aim of the present study was to evaluate the body weight evolution in obese patients admitted for a 2-week residential program and followed-up on ambulatory basis, as well as to evaluate factors having impact on weight evolution after 5 years.

Methods

Thirty-nine obese patients participated in a 2-week structured interdisciplinary weight loss program, involving individual and group therapies, and including physical activity, nutritional education and standard cognitive-behavioral techniques. Patients were then followed-up regularly by their general practitioners for 5 years.

Results

After 5 years, 33 subjects completed the study. Seventy percent of the patients lost weight or maintained their weight loss. Total score for dietary structure, eating behavior disorders, dietary surveillance and weight management strategies, as evaluated by a validated questionnaire, was significantly lower in the weight loss group (22.4 ± 4.3) as compared to maintenance group (24.4 ± 6.1, p < 0.05) and regain group (29.7 ± 4.0, p < 0.01). Patients who lost weight presented a more important follow-up on long-term weight management (p < 0.05), a better dietary results (p < 0.01) as well as more physical activity (p < 0.05) that the regain group.

Conclusion

The present study demonstrated that an initial multidimensional and multidisciplinary in-hospital program with a consecutive long-term ambulatory follow-up may lead to a significant weight loss (55%) and/or weight maintenance (15%).

Practice implications

A multidisciplinary and well-designed initial treatment and long-term follow-up program is mandatory for obesity management.     

Effect of raloxifene and low-dose percutaneous 17β-estradiol on menopause symptoms and endometrium—A randomized controlled trial

Objective

To investigate the effects on climacteric symptoms and endometrium of percutaneous low-dose 17β-estradiol associated with raloxifene in postmenopausal women.

Design

randomized placebo-controlled study.

Method

Fifty-two postmenopausal women with moderate to severe hot flushes were randomized to receive either 60 mg raloxifene (RLX; n = 20), 0.5 mg percutaneous 17β-estradiol associated to 60 mg raloxifene (RLX + E₂; n = 16) or placebo (PLC; n = 16). Climacteric symptoms (Kupperman index) and vaginal bleeding were evaluated. At baseline and at the end of the study endometrial thickness was measured and endometrial samples were collected for histological study.

Results

At baseline, the mean Kupperman index was 23.7 ± 1.8 in RLX group, 22.9 ± 1.9 in RLX + E₂ group and 22.6 ± 1.9 in the placebo group (NS). After 3 months, there was a significant reduction in Kupperman index mean values in both groups, but no statistical difference was observed between groups. However, RLX + E₂ and placebo were significantly superior to RLX in reducing hot flush severity (p < 0.05). Endometrial thickness did not change in both groups. The association of percutaneous low-dose 17β-estradiol to raloxifene was not associated with proliferation of endometrium neither in hysteroscopies nor in endometrial biopsies at the third month of treatment. No vaginal bleeding was reported during the study.

Conclusions

The association of percutaneous low dose of 17β-estradiol with raloxifene exerted favorable effects on hot flushes severity of postmenopausal women, providing a safe profile in endometrium at least in short-term therapy.     

Association between the so-called “activation syndrome” and bipolar II disorder,a related disorder,and bipolar suggestive features in outpatients with depression

Background

Activation syndrome (AS) is a cluster of symptoms listed by the US Food and Drug Administration as possible suicidality precursors during antidepressant treatment. We aimed to clarify whether AS is associated with bipolar II disorder (BP-II) and its related disorder, i.e., bipolar disorder not otherwise specified (BP-NOS), which are often mistreated as major depressive disorder (MDD), as well as bipolar suggestive features in outpatients with depression.

Methods

The frequency of AS, bipolar suggestive features, and background variables in consecutive outpatients with a major depressive episode (MDE) due to BP-II/BP-NOS or MDD, who were naturalistically treated with antidepressants, were investigated and analyzed retrospectively.

Results

Of 157 evaluable patients (46 BP-II/BP-NOS, 111 MDD), 39 (24.8%) experienced AS. Patients with BP-II/BP-NOS experienced AS significantly more frequently than patients with MDD (52.2% of BP-II/BP-NOS vs. 13.5% of MDD, p<0.01). Univariate analysis revealed that BP-II/BP-NOS diagnosis, cyclothymic temperament, early age at onset of first MDE, psychiatric comorbidities, and depressive mixed state (DMX) were significantly associated with AS development in the entire sample. Multivariate analysis revealed that BP-II/BP-NOS diagnosis and DMX were independent risk factors for AS.

Limitations

This is a retrospective and naturalistic study; therefore, patient selection bias could have occurred.

Conclusions

Cautious monitoring of AS is needed during antidepressant trials in patients with BP-II/BP-NOS. Clinicians should re-evaluate underlying bipolarity when they confront AS. Antidepressants should be avoided for treating a current DMX beyond the unipolar–bipolar dichotomy. Prospective studies are needed to confirm these results.     

Combined dexamethasone suppression–corticotrophin-releasing hormone stimulation test in medication-free major depression and healthy volunteers

Background

The hypothalamic–pituitary–adrenal (HPA) axis is dysfunctional in a subgroup of mood disorders.

Methods

We compared cortisol and adrenocorticotropic hormone (ACTH) responses in major depression and healthy volunteers to the combined dexamethasone suppression–corticotrophin-releasing hormone stimulation (DEX–CRH) test. Unlike other published studies, the study patients were medication-free and the healthy volunteers did not have first-degree relatives with a mood or psychotic disorder. Demographics, DSM-IV diagnoses and other clinical parameters were evaluated in major depressive disorder (MDD) and healthy control groups. Participants received an oral dose of 1.5 mg dexamethasone at 11 pm the day before CRH administration. On the following day, at 3 pm, 100 µg of ovine CRH was infused. Blood samples for determination of cortisol and ACTH were collected every 15 min from 3 pm to 4:15 pm. Cortisol and ACTH responses were calculated as areas under the curve.

Results

Controlling for age, baseline (i.e., post-dexamethasone) ACTH levels were higher in depressed patients compared to controls (p=0.01). There was a trend for higher ACTH responses in depressed patients compared to the control group (p=0.08). In depressed patients, cortisol and ACTH responses correlated positively with age, duration of illness and number of hospitalizations.

Limitations

Because of the cross-sectional study design we can only evaluate the nature of potential HPA axis disturbances that were present in patients when they are acutely depressed.

Conclusions

Feedback inhibition of ACTH secretion by cortisol is compromised in MDD, and this is independent of an age effect on the HPA axis function.