Short-term Antidepressant Treatment Research Articles

The interaction of P11 methylation and early-life stress impacts the antidepressant response in patients with major depressive disorder

PurposeThe present research investigates the influence of P11 gene DNA methylation combined with life stress on the response to antidepressants in the first two weeks. MethodsA total of 291 Han Chinese patients with major depressive disorder and 100 healthy controls were included. The Life Events Scale and the Childhood Trauma Questionnaire were used to assess stress. The primary endpoint was the Hamilton Depression Rating Scale-17 reduction rate after two weeks of treatment. The Illumina HiSeq Platform was used to detect the methylation of 74 CpG sites of the P11 gene in peripheral blood samples. ResultsThe mean methylation of all P11 CpG sites, as well as the methylation at 4 CpG sites (P11-2-169, P11-2-192, P11-2-202, P11-2-204), were significantly higher in patients with MDD than in healthy controls (FDR-corrected P < 0.05). The response to antidepressants was associated with the following interactions: the CTQ score and P11-3-185 site methylation (OR = 0.297, FDR-corrected P = 0.023), the CTQ physical neglect score and P11-2-117 site methylation (OR = 0.005, FDR-corrected P = 0.033), and the CTQ emotional abuse score and P11-3-185 site methylation (OR = 0.001, FDR-corrected P = 0.023). ConclusionsThe methylation of the P11 gene was significantly higher in patients with major depressive disorder. The interaction of P11 DNA methylation and early-life stress may influence the short-term antidepressant treatment response.

Electroencephalographic Network Topologies Predict Antidepressant Responses in Patients With Major Depressive Disorder.

Medication therapy seems to be an effective treatment for major depressive disorder (MDD). However, although the efficacies of various medicines are equal or similar on average, they vary widely among individuals. Therefore, an understanding of methods for the timely evaluation of short-term therapeutic response and prediction of symptom improvement after a specific course of medication at the individual level at the initial stage of treatment is very important. In our present study, we sought to identify a neurobiological signature of the response to short-term antidepressant treatment. Related brain network analysis was applied in resting-state electroencephalogram (EEG) datasets from patients with MDD. The corresponding EEG networks were constructed accordingly and then quantitatively measured to predict the efficacy after eight weeks of medication, as well as to distinguish the therapeutic responders from non-responders. The results of our present study revealed that the corresponding resting-state EEG networks became significantly weaker after one week of treatment, and the eventual medication efficacy was reliably predicted using the changes in those network properties within the one-week medication regimen. Moreover, the corresponding resting-state networks at baseline were also proven to precisely distinguish those responders from other individuals with an accuracy of 96.67% when using the spatial network topologies as the discriminative features. These findings consistently provide a deeper neurobiological understanding of antidepressant treatment and a reliable and quantitative approach for personalized treatment of MDD.

The relationship of tryptophan hydroxylase-2 methylation to early-life stress and its impact on short-term antidepressant treatment response

IntroductionThe gene tryptophan hydroxylase 2 (TPH2) encodes the associated rate-limiting enzyme in the biosynthesis 5-HT (serotonin). Early life stress and adult variability in TPH2 can correspond with diminished response to antidepressants for patients with major depressive disorder (MDD). DNA methylation is an epigenetic mechanism mediating gene expression, often tempered by environmental factors. Here, we investigate the influence of TPH2 methylation combined with stress on response to antidepressants within the first two weeks of treatment initiation. Methods291 Han Chinese patients with major depressive disorder and 100 healthy controls comprised the study population. The Life Events Scale (LES) and the Childhood Trauma Questionnaire (CTQ) rated recent and early-life stress. The primary outcome equaled a reduction by ≥ 50% from the Hamilton Depression Rating Scale-17 (HAMD-17) after 2 weeks of treatment. The Illumina HiSeq platform assessed methylation status in 38 CpG sites located upstream and downstream of 11 TPH2 polymorphism sites. ResultsIn 291 patients and 100 healthy controls, 3 CpG sites predict antidepressant treatment response per sex (TPH2-7-142, p=0.012; TPH2-1-43, p=0.033; TPH2-5-203, p=0.036). High-level CTQ scores relate significantly to DNA hypomethylation at CpG-site TPH2-8-237 in males (false discovery rate [FDR]-corrected p=0.038). Additionally, the interaction of hypermethylation in two CpG sites and elevated early-life stress may reduce antidepressant response (TPH2-5-203, FDR corrected p=0.010; TPH2-10-60, FDR corrected p=0.001). ConclusionsOur study suggests that TPH2 methylation and its interaction with early-life stress may impair antidepressant response, suggesting that pharmaco-epigenetic studies could identify epigenetic biomarkers for antidepressant response.

PND1 USE OF CLINICAL GLOBAL IMPRESSIONS-SEVERITY (CGI-S) TO ASSESS RESPONSE TO ANTIDEPRESSANT TREATMENT IN PATIENTS WITH TREATMENT-RESISTANT DEPRESSION

Montgomery-Åsberg Depression Rating Scale (MADRS), a 10-item questionnaire (each scored on a 7-point scale [0-6]) is a validated tool for physicians to determine response to antidepressant treatment and is used widely in clinical trial settings. The Clinical Global Impressions-Severity (CGI-S) scale with one question scored on a 7-point response scale is a more practical tool for clinicians in real-world practice. The appropriateness of using CGI-S-based assessment for identifying responders to short-term antidepressant treatment among patients with treatment-resistant depression (TRD) was determined by evaluating agreement with the established MADRS-based assessment of response.

Short-term antidepressant treatment has long-lasting effects, and reverses stress-induced decreases in bone features in rats

Antidepressants are among the most-prescribed class of drugs in the world and though weight gain is a common outcome of antidepressant treatment, that effect is not well understood. We employed an animal model comprised of 2 weeks of chronic restraint stress with antidepressant treatment, followed by diet-induced obesity. We showed that short-term antidepressant treatment had long-lasting effects, not only leading to weight gain, but also enhancing trabecular and cortical bone features in rats; therefore, weight gain in this model was different from that of the classic diet-induced obesity. Late in the post-restraint recovery period, antidepressant-treated animals were significantly heavier and had better bone features than saline-treated controls, when assessed in the distal femoral metaphysis. The propensity to gain weight might have influenced the rate of catch-up growth and bone allometry, as heavier animals treated with fluoxetine also had enhanced bone features when compared to non-stressed animals. Therefore, short-term antidepressant treatment ameliorated the long-term effects of stress on body growth and bone. Growth and bone structural features were associated with leptin levels, and the interaction between leptin levels and antidepressant was significant for bone mineral content, suggesting that short-term antidepressants in the context of long-term diet-induced obesity modified the role of leptin in bone formation. To our knowledge this is the first study reporting that short-term antidepressant treatment has long-lasting effects in restoring the effects of chronic stress in body weight and bone formation. Our findings may be relevant to the understanding and treatment of osteoporosis, a condition of increasing prevalence due to the aging population.

Variation in response to short-term antidepressant treatment between patients with continuous and non-continuous cycling bipolar disorders

ObjectivesThe study aimed to compare effectiveness and safety of short-term antidepressant treatment between patients with continuous (CCC) and non-continuous (N-CCC) cycling bipolar disorders. MethodsThe study sample included 101 patients with bipolar disorder, 22 (21.8%) CCC and 79 (78.2%) N-CCC. Response was defined as a HDRS21 total score <7 at 12 weeks of treatment and remission as a ≥50% reduction of baseline HDRS21 total score sustained for 8 weeks. ResultsCompared with N-CCC patients, CCC patients achieved a significantly lower percentage of response (respectively 50% vs. 82.3%, χ²=9.6, p=0.002) and remission (respectively 40.9% vs. 69.6%, χ²=6.11, p=0.013). Adjusted logistic regression analysis indicated that CCC patients were 4.3 times more likely to be non-responders and 3.3 times more likely to be non-remitters than N-CCC patients. ConcerningAD safety, 1 (5.0%) CCC patient committed a suicide attempt and AD-emerging switch was observed in 2 patients with N-CCC (2.5%) and in 1 with CCC (4.5%). LimitationsThe observational nature of the study, retrospective assessment of course, and unblinded outcomes assessment. ConclusionsOur findings indicate that the presence or absence of a free interval identifies two different forms of bipolar disorders with different response not only to prophylactic treatment, as previously reported, but also to short-term ADs. We submit that clinicians should take into consideration their patients׳ pattern of cycling when prescribing short-term AD treatment. Moreover, subtypes of bipolar disorders might be used as moderators of treatment response in studies assessing the efficacy or the effectiveness of antidepressant treatment.

Short-term antidepressant treatment of bipolar depression: Are ISBD recommendations useful in clinical practice?

ObjectivesThe study aimed to test the effectiveness of the ISBD Guidelines for short-term AD treatment of BP depression. MethodsThe study sample included 255 patients with mood disorders (154 UP, 49 BP-I, 52 BP-II). Response was defined as a HDRS21 total score<7 at 12 weeks of treatment and remission as a ≥50% reduction of baseline HDRS21 total score sustained for 8 weeks. ResultsResponse was achieved by 64.9% of patients with UP disorder, 75.5% of patients with BP-I disorder and 75.0% with BP-II disorder without significant differences (χ²=3.0, p=0.219). The remission rate did not differ significantly among groups (χ²=3.8, p=0.151). The dropout rate was significantly higher for patients with UP (18.2%) than for patients with BP-I (2%) and BP-II (7.7%) disorder (χ²=10.1, p=0.006). Concerning AD safety, one patient with BP-I depression committed a suicide attempt and AD-emerging switch was observed in 2.9% of patients, 2 with BP-I and 1 with BP-II disorder. LimitationsThe observational nature of the study and unblinded outcomes assessment. ConclusionsOur findings confirm the usefulness of ISBD Guidelines for short-term AD treatment of BP depression. These patients appear to have similar response and remission rate to those observed in UP depression and do not exhibit significant switch rates or risk of suicide. Our results are limited to patients with pure bipolar depression (excluding those with broadly defined mixed states), treated with ADs-mood stabilizers combination. We suggest to partially modify ISBD Recommendations 1 and 4, to include potential responders and to improve safety.

Paradoxical effects of short-term antidepressant treatment in fMRI emotional processing models in volunteers with high neuroticism – CORRIGENDUM

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The change of insulin levels after six weeks antidepressant use in drug-naïve major depressive patients

BackgroundA reciprocal relationship between diabetes risk and depression has been reported. There are few studies investigating glucose–insulin homeostasis before and after short-term antidepressant treatment in drug-naïve major depressive disorder (MDD) patients. MethodsThis study included 104 healthy controls and 50 drug-naïve MDD patients diagnosed according to the DSM-IV criteria. These MDD patients were randomly assigned to receive fluoxetine or venlafaxine for six weeks. Depressive symptoms, body mass index, fasting plasma levels of glucose and insulin were measured. ResultsCompared to the healthy controls, the fasting plasma insulin and the homeostasis model of assessment for pancreatic β-cell secretory function (HOMA-β) was significantly lower in the MDD patients before antidepressant treatment (7.7±4.8μIU/mL vs. 5.1±4.2μIU/mL, p=0.006; 114.2±72.3% vs. 74.8±52.0%, p=0.005, respectively). However, these indices were not correlated with depression severity. After 6 weeks of fluoxetine or venlafaxine treatment, the level of HOMA-β borderline significantly increased (108.1±75.5%, p=0.059). LimitationsThe study was limited by the follow-up duration and lack of a placebo group. ConclusionsAntidepressants might affect insulin secretion independently of the therapeutic effects on MDD. Further studies are needed to investigate the long-term effects of antidepressants on insulin regulation in MDD patients.

Paradoxical effects of short-term antidepressant treatment in fMRI emotional processing models in volunteers with high neuroticism

Short-term antidepressant administration has been reported to decrease amygdala response to threat in healthy volunteers and depressed patients. Neuroticism (N) is a risk factor for depression but has also been associated with slow or incomplete remission with antidepressant drug treatment. Our aim was to investigate early selective serotonin reuptake inhibitor (SSRI) administration neural effects on implicit processing of fearful facial expressions in volunteers with high levels of N. Highly neurotic subjects received 20 mg/day citalopram versus placebo for 7 days in a double-blind, between-groups design. On the last day haemoperfusion and functional magnetic resonance imaging (fMRI) data during a gender discrimination task with fearful and happy faces were acquired. A control group of non-neurotic volunteers was also tested. High-N volunteers had reduced responses to threatening facial expressions across key neural circuits compared to low-N volunteers. SSRI treatment was found to elevate resting perfusion in the right amygdala, increase bilateral amygdalae activation to positive and negative facial expressions and increase activation to fearful versus happy facial expressions in occipital, parietal, temporal and prefrontal cortical areas. These results suggest that 7 days of SSRI administration can increase neural markers of fear reactivity in subjects at the high end of the N dimension and may be related to early increases in anxiety and agitation seen early in treatment. Such processes may be involved in the later therapeutic effects through decreased avoidance and increased learning about social 'threat' cues.

Effect of short-term antidepressant treatment on early maladaptive schemas in patients with major depressive and panic disorder

Objective. We aimed to investigate the effect of anti-depressant treatment on early maladaptive schemas (EMSs). Methods. Eighty patients were self-referred to a psychiatric outpatient clinic and were diagnosed with major depressive disorder (MDD) (n = 40) and panic disorder (PD) (n = 40) according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV-TR). These patients were administered the Beck Depression Inventory (BDI), the Beck Anxiety Inventory (BAI) and the Young Schema Questionnaire-Short Form (YSQ-SF) before and after a 2-month period of antidepressant treatment and were compared with 40 healthy control subjects. Results and Conclusion. Depressive mood states were more likely to activate early maladaptive schemas compared to the anxious mood states, and treating these mood states simply with anti-depressive medications led to significant improvements in the activation of these schemas. We concluded that half of the schemas might be accepted as antidepressant treatment-resistant EMSs, or, in other words, they can be viewed in part as those specific to depressive mood states.

Long-term body weight outcomes of antidepressant–environment interactions

Both obesity rates and antidepressant use have escalated in the last 20 years. Most people who start antidepressant treatment discontinue it on their own. Meanwhile, obesity rates continue to increase. To test the hypothesis that antidepressant use is a risk factor for obesity, even after long-term discontinuation, we developed a novel animal paradigm consisting of short-term exposure to stress and antidepressants, followed by long-term high-fat diet. We show here that recurrent restraint stress (RRS)-related weight loss is recovered 2 weeks after the end of stress in young growing rats receiving a high-fat diet. It is noteworthy that animals that received short-term antidepressant treatment with either imipramine or fluoxetine during 7 days of RRS showed behavioral evidence of antidepressant effects. When exposed to a high-fat diet after stress and when antidepressant treatment had ended, the animals had significant increases in caloric intake, body weight (BW) and size from 17 to 22 weeks following antidepressant discontinuation when compared with (control) RRS animals treated with saline and fed with a high-fat diet. These data are consistent with the previously described phenomenon of time-dependent sensitization, and support the notion that enduring effects of short-term antidepressant treatment become manifest on a long-term basis after antidepressant discontinuation, during conditions of high stress followed by high-fat intake. Analyses of open field and body size measurements obtained in a small subset of animals show that animals previously exposed to antidepressant had no deficits in locomotor activity and were larger. Antidepressant exposure may therefore be a covert, insidious and enduring risk factor for obesity, even after discontinuation of antidepressant treatment. Our data support the concept of persistent, long-term effects of pharmacological–environment interactions on BW regulation.

P01-92 - Early changes are associated with late changes of BDNF serum levels in inpatients with major depression during short-term antidepressant treatment

ObjectivesMean BDNF serum concentration is lower in patients with major depression (MD) as compared to healthy controls. BDNF increases during the course of antidepressant treatment. This increase has been associated with symptom amelioration. The aim of this study was to analyse the relation between early and late BDNF changes during antidepressant treatment.MethodsForty-six patients with MD according to DSM-IV were included for this study. Patients were treated as clinically indicated. Depression severity was assessed by HAMD-17 by trained raters from baseline to week 6 in weekly intervals. Serum at each visit (baseline, V1-V6) was obtained from whole blood after centrifugation with 1.000 × g for 15 minutes. Aliquots were frozen at −80°C until analysis. BDNF serum concentration was determined with ELISA (R&amp;D Systems). We analysed correlations between early changes of BDNF level (baseline to weeks 1 and 2) with BDNF changes in the later course of treatment (change from baseline to weeks 4, 5 and 6). Further, the association between early and late BDNF changes was calculated by means of linear regression analysis.ResultsThere was a high correlation between BDNF changes in the early course of treatment and final BDNF changes (p&lt; 0.05 for each analysis). Early BDNF changes accounted for a high percentage of the variance of late BDNF changes (p&lt; 0.05 for each analysis).ConclusionsThese results suggest that an early change of BDNF serum level is predictive for BDNF change in the later course of antidepressant treatment in patients with Major Depression.

Evaluation of the effect of selective serotonin-reuptake inhibitors on lymphocyte subsets in patients with a major depressive disorder

To date, only the effect of a short-term antidepressant treatment (<12 weeks) on neuroendocrinoimmune alterations in patients with a major depressive disorder has been evaluated. Our objective was to determine the effect of a 52-week long treatment with selective serotonin-reuptake inhibitors on lymphocyte subsets. The participants were thirty-one patients and twenty-two healthy volunteers. The final number of patients (10) resulted from selection and course, as detailed in the enrollment scheme. Methods used to psychiatrically analyze the participants included the Mini-International Neuropsychiatric Interview, Hamilton Depression Scale and Beck Depression Inventory. The peripheral lymphocyte subsets were measured in peripheral blood using flow cytometry. Before treatment, increased counts of natural killer (NK) cells in patients were statistically significant when compared with those of healthy volunteers (312+/-29 versus 158+/-30; cells/mL), but no differences in the populations of T and B cells were found. The patients showed remission of depressive episodes after 20 weeks of treatment along with an increase in NK cell and B cell populations, which remained increased until the end of the study. At the 52nd week of treatment, patients showed an increase in the counts of NK cells (396+/-101 cells/mL) and B cells (268+/-64 cells/mL) compared to healthy volunteers (NK, 159+/-30 cells/mL; B cells, 179+/-37 cells/mL). We conclude that long-term treatment with selective serotonin-reuptake inhibitors not only causes remission of depressive symptoms, but also affects lymphocyte subset populations. The physiopathological consequence of these changes remains to be determined.

P.1.a.009 Impulsivity and the C(-1019)G functional polymorphism of the HTR1A gene

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).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.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.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.

Short-term antidepressant treatment modulates amygdala response to happy faces

We have previously demonstrated that antidepressant medication facilitates the processing of positive affective stimuli in healthy volunteers. These early effects of antidepressants may be an important component in the therapeutic effects of antidepressant treatment in patients with depression and anxiety. Here we used functional magnetic resonance imaging in a double-blind, randomised, placebo-controlled between-groups design to investigate the effects of short-term (7-10 days) treatment with the selective serotonin reuptake inhibitor, citalopram, on the amygdala response to positive and negative facial expressions in healthy volunteers. Citalopram was associated with increased amygdala activation to happy faces relative to placebo control, without changes in levels of mood or anxiety. These early, direct effects of antidepressant administration on emotional processing are consistent with a cognitive neuropsychological model of antidepressant action.

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.

Does maternal role functioning improve with antidepressant treatment in women with postpartum depression?

The ability to mother her infant is reduced in a woman with postpartum depression (PPD). Although antidepressant treatment effectively improves depressive symptoms, various domains of functioning, for example, work and relationships, do not universally improve with treatment. In this pilot study, we investigated whether maternal role functioning improved with antidepressant treatment in women with PPD. The pilot study was an exploratory analysis of a larger study. A subset of women (n = 27) from a randomized clinical trial (double-blind, 8-week trial of nortriptyline compared with sertraline) completed three outcome measures of maternal role functioning: gratification in the maternal role, the Infant Care Survey (ICS), and videotapes of maternal-infant interaction. The tapes were analyzed using the Child and Caregiver Mutual Regulation Coding Scale and Noldus Behavioral Coding Software. The two antidepressants were equally efficacious in decreasing depressive symptoms and improving overall functioning and gratification in the maternal role. Differences between times 1 and 2 in the mother-infant interactions were related to time (increasing age of the infant) and not assignment of antidepressant or remission of depression. Effective treatment with two antidepressants improves gratification in the maternal role but not self-efficacy or maternal-infant interaction in women with PPD. Results of the study can help women and their healthcare providers to weigh the benefits of short-term antidepressant treatment in the postpartum period. Future studies should consider outcomes related to a longer duration of treatment.

Treatment of Rapid-Cycling Bipolar Disorder: Are Antidepressants Mood Destabilizers?

Treatment of Rapid-Cycling Bipolar Disorder: Are Antidepressants Mood Destabilizers?

A monoamine oxidase B gene variant and short-term antidepressant treatment response

Genetic differences among patients suffering from Major Depression are likely to contribute to interindividual differences in medication treatment response. Thus, the identification of gene variants affecting drug response is needed in order to be able to predict response to psychopharmacological drugs. This study analyzed a possible association of the common A644G single nucleotide polymorphism (SNP) within intron 13 of the monoamine oxidase B (MAOB) gene with antidepressant treatment response. The study population consisted of n = 102 patients with major depression (criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition; DSM-IV) participating in a randomized double-blind controlled clinical trial, conducted at 50 centers in Germany, comparing the efficacy of mirtazapine and paroxetine during 6 weeks of treatment. Overall, female patients homozygous for the A-allele had a significantly faster and more pronounced antidepressant treatment response than AG/GG-carriers. In paroxetine-treated females these differences remained statistically significant. In mirtazapine-treated females homozygous for the A-allele compared to AG/GG-carriers, HAMD-17 scores during the study period were constantly and markedly lower, but not statistically different. In males, we found no association between the MAOB A644G intron 13 SNP and antidepressant treatment response. Our data provide first suggestive evidence that the MAOB A644G SNP is involved in the outcome of treatment with mirtazapine or paroxetine in females with major depression. To confirm the role of the MAOB A644G gene variant in antidepressant treatment response, independent replications are needed. If replicated, the MAOB A644G polymorphism could be considered useful for prospective confirmatory pharmacogenetic trials in patients with major depression.