Strategic use of new generation antidepressants for depression: SUN(^_^)D study protocol

<p>Abstract</p> <p>Background</p> <p>After more than half a century of modern psychopharmacology, with billions of dollars spent on antidepressants annually world-wide, we lack good evidence to guide our everyday decisions in conducting antidepressant treatment of patients with major depression. First we did not know which antidepressant to use as first line treatment. Second we do not know which dosage we should be aiming at with that antidepressant. Because more than half of the patients with major depression starting treatment do not remit after adequate trial with the first agent, they will need a second line treatment. Dose escalation, augmentation and switching are the three often recommended second line strategies but we do not know which is better than the others. Moreover, we do not know when to start considering this second line treatment.</p> <p>The recently published multiple-treatments meta-analysis of 12 new generation antidepressants has provided some partial answers to the first question. Starting with these findings, this proposed trial aims to establish the optimum 1st line and 2nd line antidepressant treatment strategy among adult patients with a non-psychotic unipolar major depressive episode.</p> <p>Methods</p> <p>SUN(^_^)D, the Strategic Use of New generation antidepressants for Depression, is an assessor-blinded, parallel-group, multi-centre randomised controlled trial. Step I is a cluster-randomised trial comparing titration up to the minimum vs maximum of the recommended dose range among patients starting with sertraline. The primary outcome is the change in the Patient Health Questionnaire (PHQ)-9 scores administered by a blinded rater via telephone at week 1 through 3. Step II is an individually randomised trial comparing staying on sertraline, augmentation of sertraline with mirtazapine, and switching to mirtazapine among patients who have not remitted on the first line treatment by week 3. The primary outcome is the change in the PHQ-9 scores at week 4 through 9. Step III represents a continuation phase to Steps I and II and aims to establish longer-term effectiveness and acceptability of the above-examined treatment strategies up to week 25. The trial is supported by the Grant-in-Aid by the Ministry of Health, Labour and Welfare, Japan.</p> <p>Discussion</p> <p>SUN(^_^)D promises to be a pragmatic large trial to answer important clinical questions that every clinician treating patients with major depression faces in his/her daily practices concerning its first- and second-line treatments.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01109693">NCT01109693</a></p

Paroxetine reduces crying in young women watching emotional movies

Rationale: Crying is a unique human emotional reaction that has not received much attention from researchers. Little is known about its underlying neurobiological mechanisms, although there is some indirect evidence suggesting the involvement of central serotonin. Objectives: We examined the acute effects of the administration of 20 mg paroxetine on the crying of young, healthy females in response to emotional movies. Methods: We applied a double-blind, crossover randomised design with 25 healthy young females as study participants. On separate days, they received either paroxetine or placebo and were exposed to one of two emotional movies: 'Once Were Warriors' and 'Brian's Song'. Crying was assessed by self-report. In addition, the reactions to emotional International Affective Picture System (IAPS) pictures and mood were measured. Results: Paroxetine had a significant inhibitory effect on crying. During both films, the paroxetine group cried significantly less than the placebo group. In contrast, no effects on mood and only minor effects on the reaction to the IAPS pictures were observed. Conclusions: A single dose of paroxetine inhibits emotional crying significantly. It is not sure what the underlying mechanism is. However, since there was no effect on mood and only minor effects on the response to emotional pictures, we postulate that paroxetine mainly acts on the physiological processes involved in the crying response

Treatment patterns associated with Duloxetine and Venlafaxine use for Major Depressive Disorder

<p>Abstract</p> <p>Background</p> <p>Duloxetine and venlafaxine extended release (venlafaxine XR) are SNRIs indicated for the treatment of MDD. This study addresses whether duloxetine and venlafaxine XR are interchangeable in their patterns of use with patients who are depressed or are used more selectively based on treatment history, background characteristics, and presenting symptoms.</p> <p>Methods</p> <p>This was a retrospective analysis of an administrative insurance claims database. We studied patients in managed care with major depressive disorder (MDD) treated with duloxetine or venlafaxine XR. Predictors of treatment and cost were assessed using Chi-square and logistic regression analyses of demographics and past-year medication use and comorbidities.</p> <p>Results</p> <p>Patients with MDD treated with duloxetine (n = 9,641) versus venlafaxine XR (n = 8,514) tended to be older, slightly more likely to be female, and treated by a psychiatrist (<it>P </it>< 0.0001). In the prior year, more duloxetine patients (vs. venlafaxine XR) received ≥3 unique antidepressants (20.8% vs. 16.6%), ≥3 unique pain medications (25.5% vs. 15.6%), and had ≥8 unique diagnosed comorbid medical and psychiatric conditions (38.6% vs. 29.1%). The prior 6-month total health care costs were $1,731 higher for duloxetine than for venlafaxine XR and declined for both medications in the 6 months after treatment began. Logistic regression analysis revealed that 61% of duloxetine patients and 61% of venlafaxine XR patients were predictable from prior patient and treatment factors.</p> <p>Conclusions</p> <p>Patients with MDD treated with duloxetine tended to have a more complex and costly antecedent clinical presentation compared with venlafaxine XR patients, suggesting that physicians do not use the medications interchangeably.</p

Dopamine precursor depletion improves punishment prediction during reversal learning in healthy females but not males

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The Brain Reaction to Viewing Faces of Opposite- and Same-Sex Romantic Partners

We pursued our functional magnetic resonance imaging (fMRI) studies of the neural correlates of romantic love in 24 subjects, half of whom were female (6 heterosexual and 6 homosexual) and half male (6 heterosexual and 6 homosexual). We compared the pattern of activity produced in their brains when they viewed the faces of their loved partners with that produced when they viewed the faces of friends of the same sex to whom they were romantically indifferent. The pattern of activation and de-activation was very similar in the brains of males and females, and heterosexuals and homosexuals. We could therefore detect no difference in activation patterns between these groups

Vitamin B12 status in patients of Turkish and Dutch descent with depression: A comparative cross-sectional study

Background: Studies have shown a clear relationship between depressive disorders and vitamin B12 deficiency. Gastroenteritis and Helicobacter pylori infections can cause vitamin B12 deficiency. Helicobacter pylori infections are not uncommon among people of Turkish descent in The Netherlands. Aim: To examine the frequency of vitamin B12 deficiency in depressive patients of Turkish descent and compare it to the frequency of vitamin B12 deficiency in depressive patients of Dutch descent. Methods: The present study is a comparative cross-sectional study of 47 patients of Turkish descent and 28 of Dutch descent. The depressive disorder diagnosis and differential diagnosis were made using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, fourth edition text revision (SCID). The severity of the depressive symptoms was determined using the Beck Depression Inventory (BDI) and the 21-item Hamilton Depression Rating Scale (HAM-D-21). Serum baseline vitamin B6 and B12, folic acid and total serum homocysteine (tHcy) levels were measured. Results: The average ages of the patients of Turkish and Dutch descent were 40.57 and 44.75 years, respectively. There were no demonstrable differences between the serum vitamin B6, folic acid and tHcy levels in the two groups. The serum vitamin B12 levels were however clearly lower in the patients of Turkish descent than in those of Dutch descent. Vitamin B12 deficiency was however observed in 14 patients of Turkish descent and 1 of Dutch descent. This difference was significant. On the BDI, the patients of Turkish descent scored significantly higher than those of Dutch descent. Patients with vitamin B12 deficiency and those with hyperhomocysteinaemia had a significantly higher BDI score than patients with normal vitamin B12 and homocysteine levels. No relationship was observed with vitamin B12 and tHcy. Conclusion: Vitamin B12 deficiency occurs more frequently in depressive patients of Turkish than of Dutch descent. This is why it is advisable to test the vitamin B12 serum level in depressive patients of Turkish descent

Consistent superiority of selective serotonin reuptake inhibitors over placebo in reducing depressed mood in patients with major depression.

The recent questioning of the antidepressant effect of selective serotonin reuptake inhibitors (SSRIs) is partly based on the observation that approximately half of company-sponsored trials have failed to reveal a significant difference between active drug and placebo. Most of these have applied the Hamilton depression rating scale to assess symptom severity, the sum score for its 17 items (HDRS-17-sum) serving as effect parameter. In this study, we examined whether the negative outcomes of many SSRI trials may be partly caused by the use of this frequently questioned measure of response. We undertook patient-level post-hoc analyses of 18 industry-sponsored placebo-controlled trials regarding paroxetine, citalopram, sertraline or fluoxetine, and including in total 6669 adults with major depression, the aim being to assess what the outcome would have been if the single item depressed mood (rated 0-4) had been used as a measure of efficacy. In total, 32 drug-placebo comparisons were reassessed. While 18 out of 32 comparisons (56%) failed to separate active drug from placebo at week 6 with respect to reduction in HDRS-17-sum, only 3 out of 32 comparisons (9%) were negative when depressed mood was used as an effect parameter (

Affective regulation of cognitive-control adjustments in remitted depressive patients after acute tryptophan depletion

Negative affect in healthy populations regulates the appraisal of demanding situations, which tunes subsequent effort mobilization and adjustments in cognitive control. In the present study, we hypothesized that dysphoria in depressed individuals similarly modulates this adaptation, possibly through a neural mechanism involving serotonergic regulation. We tested the effect of dysphoria induced by acute tryptophan depletion (ATD) in remitted depressed patients on conflict adaptation in a Simon task. ATD temporarily lowers the availability of the serotonin precursor L-Tryptophan and is known to increase depressive symptoms in approximately half of remitted depressed participants. We found that depressive symptoms induced by ATD were associated with increased conflict adaptation. Our finding extends recent observations implying an important role of affect in regulating conflict-driven cognitive control

Which patient will feel down, which will be happy? The need to study the genetic disposition of emotional states

Purpose In quality-of-life (QL) research, the genetic susceptibility of negative and positive emotions is frequently ignored, taken for granted, or treated as noise. The objectives are to describe: (1) the major findings of studies addressing the heritable and environmental causes of variation in negative and positive emotional states and (2) the major biological pathways of and genetic variants involved in these emotional states

Suicidal ideation during treatment of depression with escitalopram and nortriptyline in Genome-Based Therapeutic Drugs for Depression (GENDEP): a clinical trial

SCOPUS: ar.jinfo:eu-repo/semantics/publishe