Monoamine oxidase A variant influences antidepressant treatment response in female patients with Major Depression

The monoamine oxidase A (MAO-A) has been suggested to be involved in the pathogenesis as well as the pharmacological treatment of Major Depression. In the present study, 340 patients with a Major Depressive Episode (f=194, m=146; DSM-IV) of Caucasian descent were genotyped for the functional MAO-A VNTR. The clinical response to antidepressive pharmacological treatment was assessed by weekly intra-individual changes of HAM-D-21 scores over six weeks. The longer MAO-A alleles (3a, 4, 5) conferred a significant risk of slower and less efficient overall response over the course of 6 weeks of antidepressant treatment in patients with Major Depression, with the effect being restricted to female patients (p=0.028; corrected for multiple testing). The present results suggest that high-activity MAO-A genotypes possibly by consecutively decreased serotonin and/or norepinephrine availability negatively influence antidepressant treatment response during the first six weeks of pharmacological treatment in female patients with Major Depression.     

Prescribing selective serotonin reuptake inhibitors in older age

Apart from commercial reasons, two motivations have led to the introduction of SSRIs to replace the first and second generation antidepressants already available. One was the search for a more rational treatment, based on specific mechanisms, the other the development of effective treatments with fewer side effects, particularly for older patients, who have a greater sensitivity to cardio-vascular and central nervous system effects. The first has been frustrated up to a point, in that SSRIs and other single mechanism drugs do not appear to be more effective than the earliest relatively non-specific antidepressants. The second has been fulfilled, in that SSRIs generally are better tolerated in older patients and in overdose. However, there is a spectrum of other side effects that are particularly relevant in older age and that need attention when treating depression in this particular patient group.     

Impact of patient selection and study characteristics on signal detection in placebo-controlled trials with antidepressants

An increasing rate of antidepressant trials fail due to large placebo responses. This analysis aimed to identify variables influencing signal detection in clinical trials of major depressive disorder. Patient-level data of randomized patients with a duloxetine dose ≥60 mg/day were obtained from Lilly. Total scores of the Hamilton Depression Rating scale (HAM-D) were used as efficacy endpoints. In total, 4661 patients from 14 studies were included in the analysis. The overall effect size (ES), based on the HAM-D total score at endpoint, between duloxetine and placebo was −0.272. Although no statistically significant interactions were found, the following results for factors influencing ES were seen: a very low ES (−0.157) in patients in the lowest baseline HAM-D category and in patients recruited in the last category of the recruitment period (−0.122). A higher ES in patients recruited in centers with a site-size at but not more than 2.5 times the average site-size for the study (−0.345). Study characteristics that resulted in low signal detection in our database were: <80% study completers, a HAM-D placebo response >5 points, a high variability of placebo response (SD > 7 points HAM-D), >6 post baseline visits per study, and use of an active control drug. Simpler trial designs, more homogeneous and mid-sized study sites, a primary analysis based on a higher cutoff blinded to investigators to avoid the influence of score inflation in mild patients and, if possible, studies without an active control group could lead to a better signal detection of antidepressive efficacy.     

Reduced expression of apolipoprotein E receptor type 2 in peripheral blood lymphocytes from patients with major depressive disorder

We measured the mRNA levels of apolipoprotein E receptor type 2 (ApoER2) and very low-density lipoprotein receptor (VLDLR) in peripheral blood lymphocytes from 43 patients with major depressive disorder (27 drug-free patients and 16 medicated patients) and 43 age-matched healthy controls using a quantitative real-time RT-PCR method. The correlations between mRNA levels of both receptors and clinical variables in patients were also examined. The expression of ApoER2 mRNA, but not VLDLR, was significantly lower in patients as compared to controls, irrespective of the medication status. There was no statistically significant correlation between the reduction of ApoER2 mRNA levels and any of the clinical variables measured in patients. Results from this preliminary study suggest that the expression of ApoER2 may serve as a trait marker for major depressive disorder.     

Electroconvulsive therapy,depression, the immune system and inflammation: A systematic review

Background

The management and treatment of major depressive disorder are major public health challenges, the lifetime prevalence of this illness being 4.4%–20% in the general population. Major depressive disorder and treatment resistant depression appear to be, in part, related to a dysfunction of the immune response. Among the treatments for depression ECT occupies an important place. The underlying cerebral mechanisms of ECT remain unclear.

Quetiapine for the treatment of borderline personality disorder; an open-label study

PURPOSE: Only a few studies have commented on the use of atypical antipsychotics for the treatment of Borderline Personality Disorder (BPD) features, including affective dysregulation and aggression. We aimed at evaluating both efficacy and safety of quetiapine in a sample of consecutive BPD patients. GENERAL METHODS: 29 BPD outpatients entered, and 23 completed, a 12 week, open-label, regime of quetiapine at an average daily dosage of 540 mg (range: 400-800 mg). Efficacy assessment psychometric instruments included: Hamilton Rating Scales for Depression (HAM-D); Brief Psychiatric Rating Scale (BPRS); Global Assessment of Functioning (GAF); Clinical Global Impression Scale (CGI); and Aggression Questionnaire (AQ). FINDINGS: Both completer and intent-to-treat analysis showed that most psychometric scales' scores exhibited a highly significant (HAM-D: p=.003; BPRS Hostility and Suspiciousness subscales; CGI; GAF; AQ: all at p=.000) improvement over time. Six patients dropped out early from treatment due to side effects; quetiapine was associated with two cases of transient thrombocytopenia. CONCLUSIONS: Present findings would suggest that quetiapine may be effective for the treatment of a number of BPD features, including low mood and aggression. However, monitoring blood counts in patients receiving quetiapine seems to be justified.     

Comparison of petal of Crocus sativus L. and fluoxetine in the treatment of depressed outpatients: a pilot double-blind randomized trial

Depression is one of the most common neuropsychiatric conditions, with a lifetime prevalence approaching 17%. Although a variety of pharmaceutical agents is available for the treatment of depression, psychiatrists find that many patients cannot tolerate the side effects, do not respond adequately, or finally lose their response. On the other hand, many herbs with psychotropic effects have far fewer side effects. They can provide an alternative treatment or be used to enhance the effect of conventional antidepressants. A number of recent preclinical and clinical studies indicate that stigma and petal of Crocus sativus have antidepressant effect. Our objective was to compare the efficacy of petal of C. sativus with fluoxetine in the treatment of depressed outpatients in an 8-week pilot double-blind randomized trial. Forty adult outpatients who met the DSM- IV criteria for major depression based on the structured clinical interview for DSM- IV participated in the trial. Patients have a baseline Hamilton Rating Scale for Depression score of at least 18. In this double-blind and randomized trial, patients were randomly assigned to receive capsule of petal of C. sativus 15 mg bid (morning and evening) (Group 1) and fluoxetine 10 mg bid (morning and evening) (Group 2) for a 8-week study. At the end of trial, petal of C. sativus was found to be effective similar to fluoxetine in the treatment of mild to moderate depression (F=0.03, d.f.=1, P=0.84). In addition, in the both treatments, the remission rate was 25%. There were no significant differences in the two groups in terms of observed side effects. The present study is supportive of other studies which show antidepressant effect of C. sativus.     

Reboxetine induced erectile dysfunction and spontaneous ejaculation during defecation and micturition

This is a case report of reboxetine induced erectile dysfunction, seminal emission and ejaculation during defecation and micturition. A 44 year old male who had been suffering from depression without any sexual dysfunction was put on venlafaxine XR treatment. Due to delayed ejaculation and occasional episodes of absence of ejaculation he was switched to reboxetine. At the second week of treatment he reported erectile dysfunction and premature ejaculation, and seminal emission and ejaculation during defecation and micturition occurred later at 8th week of treatment. After he was switched to sertraline 50 mg/day, his erectile dysfunction, premature and spontaneous ejaculation symptoms subsided in 2 weeks. Although reboxetine is reported to be free of sexual side effects, individual vulnerabilities to such unwanted effects should be considered, and sexual dysfunction should be assessed thoroughly during the treatment.     

Residual symptoms in bipolar disorder: the effect of the last episode after remission

In this study it is aimed to assess interepisode residual symptoms in remitted bipolar disorder patients with a hypothesis that the last episode recovered has implications on residual symptomatology. The study was carried out with 23 bipolar patients diagnosed as mania (BP-M) and 20 bipolar patients diagnosed as depression (BP-D) in their last episode, and with 22 healthy controls in a university hospital clinic. All patients were in remission for at least 6 months. In the assessment Hamilton Depression Rating Scale (HAM-D), Young Mania Rating Scale (YMRS), Stroop Test, Auditory Verbal Learning Test (AVLT), increased latency positive-evoked potentials (P300), Global Assessment of Functioning Scale (GAF), and Social Functioning Scale (SFS) were used cross-sectionally. In affective symptomatology, the BP-M group had higher YMRS scores, and the BP-D group had higher HAM-D scores compared to the controls. P300 test results revealed low amplitude in the BP-D group. In the AVLT, verbal learning and delayed recall were significantly lower in the two bipolar groups. The Stroop tasks were not different in the groups. Concerning the SFS, social withdrawal was impaired in the two bipolar groups, whereas dependency-competency was impaired in the BP-M and employment/occupation was impaired in the BP-D group. As a conclusion, bipolar patients recovering from depressive episode may experience more impairment in daily functioning due to residual depressive symptoms and impairment of attention and memory.