Antidepressants In Major Depression Research Articles

The relationship between familial-genetic risk and pharmacological treatment in a Swedish national sample of patients with major depression, bipolar disorder, and schizophrenia.

Using Swedish registers, we examine whether the prescription of and the response to antidepressants (AD), mood stabilizers (MS), and antipsychotics (AP) in the treatment of, respectively, major depression (MD), bipolar disorder (BD), and schizophrenia (SZ), are influenced by familial-genetic risk. We examined individuals born in Sweden 1960-1995 with a first diagnosis of MD (n = 257,177), BD (n = 23,032), and SZ (n = 4248) from 2006 to 2018. Drug classes and Defined Daily Dose (DDD) were obtained from the Pharmacy register using the Anatomical Therapeutic Chemical system. We utilized the Familial Genetic Risk Scores (FGRS) calculated from morbidity risks in first- through fifth degree relatives. Treatment with antidepressants (AD) in MD, mood-stabilizers (MS) in BD, and antipsychotics (AP) in SZ were associated with significantly higher disorder-specific familial-genetic risks. Using dosage trajectory analysis of AD, MS, and AP treatment for MD, BD, and SZ, respectively, familial-genetic risk was positively associated with higher and/or increasing drug dosages over time. For MD and BD, examining cases started on the most common pharmacologic treatment class (SSRIs for MD and "other anti-epileptics" for BD), familial-genetic risks were significantly lower in those who did not versus did later receive treatment from other AD and MS classes, respectively. Higher familial-genetic risk for BD predicted switching AD medication in cases of MD. Among pharmacologically treated cases of BD, familial-genetic risk was significantly higher for those treated with lithium. In a large population-based patient cohort, we found evidence of a wide-spread association between higher familial-genetic risk and i) increased likelihood of receiving pharmacologic treatment but 2) responding more poorly to it-as indicated by a switching of medications -- and/or requiring higher doses. Further investigations into the clinical utility of genetic risk scores in the clinical managements of MD, BD, and SZ are warranted.

Pregabalin augmentation of antidepressants in major depression - results from a European multicenter study

BackgroundWe aimed to investigate the prescription pattern of pregabalin augmentation of antidepressants in major depressive disorder (MDD) and to explore variables associated with add-on pregabalin treatment. Methods1410 MDD patients participated in this naturalistic European multicenter study with retrospective assessment of treatment response. Analyses of covariance, chi-squared tests, and binary logistic regressions were accomplished to determine differences in socio-demographic and clinical characteristics between MDD patients with and without pregabalin augmentation. ResultsAdd-on pregabalin was established in 102 (7.23%) MDD patients. Compared to those without receiving pregabalin, pregabalin-treated patients were characterized by a significantly higher likelihood for older age (mean: 54.74 ± 13.08 vs 49.93 ± 14.13 years), unemployment (78.43% vs 51.23%), melancholic features (83.33% vs 58.94%), inpatient treatment (72.55% vs 31.65%), previous psychiatric hospitalizations (13.52 ± 24.82 vs 4.96 ± 19.93 weeks), any somatic comorbidity (68.63% vs 44.57%), comorbid hypertension (37.25% vs 17.51%), more severe depressive symptom severity at the onset of the current episode (mean MADRS: 37.55 ± 9.00 vs 33.79 ± 7.52), receiving augmentation/combination treatment strategies in general (mean number of psychotropic drugs: 3.64 ± 0.92 vs 2.07 ± 1.17), and with antidepressants (50.00% vs 27.91%) and antipsychotics (46.08% vs 24.08%) in particular. LimitationsDue to its observational cross-sectional study design, our patient sample might not be fully representative for MDD patients in primary care settings. ConclusionsOur findings suggest that add-on pregabalin is particularly administered in more severe/difficult-to-treat MDD conditions, whereas no association between the prescription of adjunctive pregabalin and comorbid anxiety symptoms could be determined.

Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation.

Replicated international studies have underscored the human and societal costs associated with major depressive disorder. Despite the proven efficacy of monoamine-based antidepressants in major depression, the majority of treated individuals fail to achieve full syndromal and functional recovery with the index and subsequent pharmacological treatments. Ketamine and esketamine represent pharmacologically novel treatment avenues for adults with treatment-resistant depression. In addition to providing hope to affected persons, these agents represent the first non-monoaminergic agents with proven rapid-onset efficacy in major depressive disorder. Nevertheless, concerns remain about the safety and tolerability of ketamine and esketamine in mood disorders. Moreover, there is uncertainty about the appropriate position of these agents in treatment algorithms, their comparative effectiveness, and the appropriate setting, infrastructure, and personnel required for their competent and safe implementation. In this article, an international group of mood disorder experts provides a synthesis of the literature with respect to the efficacy, safety, and tolerability of ketamine and esketamine in adults with treatment-resistant depression. The authors also provide guidance for the implementation of these agents in clinical practice, with particular attention to practice parameters at point of care. Areas of consensus and future research vistas are discussed.

On the treatment effect heterogeneity of antidepressants in major depression: A Bayesian meta-analysis and simulation study.

The average treatment effect of antidepressants in major depression was found to be about 2 points on the 17-item Hamilton Depression Rating Scale, which lies below clinical relevance. Here, we searched for evidence of a relevant treatment effect heterogeneity that could justify the usage of antidepressants despite their low average treatment effect. Bayesian meta-analysis of 169 randomized, controlled trials including 58,687 patients. We considered the effect sizes log variability ratio (lnVR) and log coefficient of variation ratio (lnCVR) to analyze the difference in variability of active and placebo response. We used Bayesian random-effects meta-analyses (REMA) for lnVR and lnCVR and fitted a random-effects meta-regression (REMR) model to estimate the treatment effect variability between antidepressants and placebo. The variability ratio was found to be very close to 1 in the best fitting models (REMR: 95% highest density interval (HDI) [0.98, 1.02], REMA: 95% HDI [1.00, 1.02]). The between-study standard deviation τ under the REMA with respect to lnVR was found to be low (95% HDI [0.00, 0.02]). Simulations showed that a large treatment effect heterogeneity is only compatible with the data if a strong correlation between placebo response and individual treatment effect is assumed. The published data from RCTs on antidepressants for the treatment of major depression is compatible with a near-constant treatment effect. Although it is impossible to rule out a substantial treatment effect heterogeneity, its existence seems rather unlikely. Since the average treatment effect of antidepressants falls short of clinical relevance, the current prescribing practice should be re-evaluated.

Association between genetic polymorphism and antidepressants in major depression: a network meta-analysis.

This network meta-analysis was conducted to compare the predictive value of eight SNPs on the efficacy of antidepressants in major depressive disorder (MDD), including 5-HTTLPR, 5HTR2A(rs6311, rs6314, rs7997012 andrs6313), 5HTR2A(rs6295), BDNF(rs6265)and 5HTTSTin2.Databases were searched for related studies published up to December 2019. A total of 16 studieswere included in thisstudy.The predictive value were evaluated by the use of the odd ratios (OR) and drawing surface under the cumulative ranking curves (SUCRA). The pairwise meta-analysis indicated that in terms of overall response ratio, the SNPs were not associated with the efficacy of antidepressants in MDD. The result of this network meta-analysis suggested that there was no significant difference in predictive value of eightSNPs on the efficacy of antidepressants in MDD. More research is needed to explore the relationship between SNPs and antidepressant response.

Melancholic features (DSM-IV) predict but do not moderate response to antidepressants in major depression: an individual participant data meta-analysis of 1219 patients.

It is sometimes clinically believed that major depression with melancholic features is more responsive to antidepressants than non-melancholic depression. Proper analysis and, therefore, valid evidence to support or refute this common clinical lore is lacking. The sample was taken from three placebo-controlled randomized trials of duloxetine, escitalopram and paroxetine (n = 1219). We conducted a two-step individual participant data meta-analysis to combine linear mixed-effects regressions modeling melancholic features as prognostic factor (variable that predicts overall response regardless of the treatments) and as effect modifier (variable that predict differential response to drug over placebo). Melancholic features represented a statistically significant prognostic factor for greater reduction in depression severity both on antidepressants and on placebo, especially after 4weeks of treatment. However, they were not an effect modifier of the antidepressant treatment through the acute phase treatment: in other words. The superiority of antidepressants over placebo was not influenced by the melancholic features. The treatment decision-making as to the benefits of antidepressant treatment for patients with major depression should not be influenced by the presence or absence of melancholic features.

Initial severity of major depression and efficacy of new generation antidepressants: individual participant data meta-analysis.

The role of baseline severity as effect modifier in various psychiatric disorders is a topic of controversy and of clinical import. This study aims to examine whether baseline severity modifies the efficacy of various antidepressants for major depression through individual participant data (IPD) meta-analysis. We identified all placebo-controlled, double-blind randomised trials of new generation antidepressants in the acute phase treatment of major depression conducted in Japan and requested their IPD through the public-private partnerships (PPPs) between the relevant academic societies and the pharmaceutical companies. The effect modification by baseline depression severity was examined through six increasingly complex competing mixed-effects models for repeated measures. We identified eleven eligible trials and obtained IPD from six, which compared duloxetine, escitalopram, mirtazapine, paroxetine or bupropion against placebo (total n = 2464). The best-fitting model revealed that the interaction between baseline severity and treatment was not statistically significant (coefficient = -0.04, 95% confidence interval: -0.16 to 0.08, P = 0.49). Several sensitivity analyses confirmed the robustness of the findings. We may expect as much benefit from antidepressant treatments for mild, moderate or severe major depression. Clinical practice guidelines will need to take these findings into consideration.

Cytokine serum levels remain unchanged during lithium augmentation of antidepressants in major depression

Lithium augmentation (LA) of antidepressants is a first-line therapy in treatment-resistant depression. Immunomodulatory effects of lithium have been described. The cytokine hypothesis of depression postulates that cytokines play a key role in the pathophysiology of depression. Concordantly, it has been shown that proinflammatory cytokine serum levels decrease during antidepressant treatment. The aim of this study was to investigate changes in cytokine serum levels during LA. Serum concentrations of the cytokines interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, tumour necrosis factor alpha, interferon-gamma, granulocyte and monocyte colony stimulating factor were measured in a total of 95 acutely depressed patients before and after four weeks of LA. Changes in cytokine levels were corrected for the confounding factors severity of depression, treatment response, lithium serum level, gender, age and body mass index in a linear mixed-model analysis. We did not find a significant change in any of the measured cytokine serum levels during LA (p > 0.05). In conclusion, our study does not support the role of cytokine serum levels as a state marker in treatment of depression with LA.

The Monoamine Oxidase Inhibitor Isocarboxazid is a Relevant Treatment Option in Treatment-Resistant Depression-Experience-Based Strategies in Danish Psychiatry

The clinical use of monoamine oxidase inhibitors (MAOIs) like isocarboxazid nowadays is most often seen with treatment resistant depression, which is in accordance with the registered indication of the National Health Service of Denmark. The clinical use, however, early became restricted and today it covers only a minority of the market for antidepressants. The aim of the present paper is to give a short overview of the clinical efficacy, to review mechanisms of action and metabolism of MAOIs, and to discuss how the side effects and interactions with these drugs may be avoided. A number of clinical trials have documented that MAOIs are effective antidepressants in major depression, including in patients with melancholic syndrome. In Denmark the combined use of nortriptyline with isocarboxazid as add-on treatment for more than 30 years has proved to be safe and efficient. MAOIs must never be combined with SSRIs and serotonergic TCAs. The normal dose of isocarboxazid may cause oedema, which can be treated with a supplement of 100-200 mg pyridoxine (vitamin B6). Isocarboxazid is metabolized by hydrolysis by the liver enzyme carboxylesterase. In contrast to most other antidepressants, the liver enzyme CYP2D6 is not involved in the metabolism of isocarboxazid, which means that it can be used in normal dose for all patients. Treatment with isocarboxazid needs precautions with a number of other drugs and the necessity to avoid certain foodstuffs containing excessive amounts of tyramine. Danish patients being treated with isocarboxazid are recommended to carry along a simple instruction, containing general advice for health personal and a list of foods to avoid. Treatment with isocarboxazid is considered to be a relevant option in treatment-resistant depression and we are today much better prepared than we were many years ago to use the drug in our rational pharmacotherapy.

EPA-1240 – Sexual dysfunction and antidepressant medications in male depressed patients

Introduction Sexual dysfunction, such as low libido, erectile dysfunction and anorgasmia, is very common in patients taking serotoninergic antidepressants (SSRIs). These adverse effects persist throughout the treatment period, are not self-limited, and drive many male patients to treatment discontinuation in order to recuperate normal sexual functioning. Objectives - Aims The purpose of the present study was to investigate the sexual function of male patients treated with antidepressants for major depression, before initiation of treatment, during treatment and two months following withdrawal of SSRIs. Methods This observational study comprised 25 male patients (age: 30–50 years) followed-up on an outpatient basis for major depression. Sexual functioning was assessed with the Arizona Sexual Experience Scale (ASEX) and depressive symptoms with the Hamilton Rating Scale for Depression (HDRS) at three time points: baseline (period free of medication), three months after starting treatment with SSRIs, and two months following antidepressant discontinuation. Paired samples t-tests were used for comparisons between numeric variables at the three time points and Spearman's correlation coefficients were calculated between factors associated with sexual dysfunction. Results Mean values ??(± SD) of ASEX and HDRS scores at the initial, second and final assessment are shown in Table 1. Initial assessment Second assessment Final assessment ASEX 17.8± 5.4 25.6±7.9* 12.9±5.8** HDRS 22.3±4.2 4.2±3.4* 7.3±5.2** Correlation coefficients between ASEX, HDRS and age at the three points of evaluation are presented in Table 2. ASEX 1 Spearman's rho Sig. (2-tailed) ASEX 2 Spearman's rho Sig. (2-tailed) ASEX 3 Spearman's rho Sig. (2-tailed) HDRS 1 0.775 HDRS 2 0.318 0.340 HDRS 3 0,719 Age 0.842 Age 0.554 0.062 Age 0.856 Conclusions Antidepressants (SSRIs) have a negative impact on sexual functioning of male depressed patients. Quality of sexual functioning is negatively associated with age and the severity of depressive symptoms before the administration of antidepressant treatment. Sexual functioning significantly improves after discontinuation of antidepressants; this improvement is even superior to the pre-treatment period of sexual functioning.

High-Frequency Repetitive Transcranial Magnetic Stimulation Accelerates and Enhances the Clinical Response to Antidepressants in Major Depression

High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) is a safe and effective treatment for major depression. However, its utility as a strategy to accelerate and improve clinical response to antidepressants is still unclear. We searched the literature from 1995 through May 2012 using EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, Scopus, and ProQuest Dissertations and Theses, and, from October 2008 until May 2012, by using MEDLINE. We included only studies written in the English language. We selected all randomized, double-blind, and sham-controlled trials on HF-rTMS used as an accelerating (add-on) strategy to antidepressants for major depression. We performed a random effects meta-analysis using odds ratios (ORs) for response and remission rates following HF-rTMS and sham rTMS. Two time points were considered: the end of the add-on HF-rTMS stimulation period (T1) and the end of the study (T2). Data were obtained from 6 randomized controlled trials (RCTs), totaling 392 subjects with major depression. For T1 (at mean ± SD 2.67 ± 0.82 weeks following start of combined rTMS + antidepressant treatment), 6 studies reported on response and 4 on remission rates. We found significantly higher response rates for active HF-rTMS (43.3%; 84/194) compared to sham rTMS (26.8%; 53/198) (OR = 2.5; 95% CI, 1.12-5.56; P = .025); however, remission rates did not differ between groups (P = .33). Heterogeneity between the included RCTs reporting data on response and remission rates at T1 was significant (response: Q5 = 11.4, P = .044, I2 = 56.12; remission: Q3 = 12.24, P = .007, I2 = 75.45). For study end (T2; at mean ± SD 6.80 ± 3.11 weeks following start of combined rTMS + antidepressant treatment), 5 studies reported on response and 4 on remission rates; overall, response rates at T2 were significantly higher for subjects receiving HF-rTMS in comparison to those receiving sham rTMS (62% [104/168] and 46% [79/172], respectively; OR = 1.9; 95% CI, 1.003-3.56; P = .049). Also, 53.8% (57/106) and 38.64% (36/107) of subjects receiving active HF-rTMS and sham rTMS, respectively, were in remission at T2 (OR = 2.42; 95% CI, 1.27-4.61; P = .007). Heterogeneity between the included RCTs reporting data on remission rates at T2 was not significant, although RCTs reporting on response rates at T2 were heterogeneous. The baseline depression scores for active and sham rTMS groups were similar. Finally, HF-rTMS was comparable to sham rTMS in terms of dropout rates. HF-rTMS is a promising strategy for accelerating clinical response to antidepressants in major depression, providing clinically meaningful benefits that are comparable to those of other agents such as triiodothyronine and pindolol. Furthermore, HF-rTMS seems to be an acceptable treatment for depressed subjects.

No Effect of Serotoninergic Gene Variants on Response to Interpersonal Counseling and Antidepressants in Major Depression

ObjectiveGene variants within the serotonin pathway have been associated with major depressive disorder (MDD) treatment outcomes, however a possible different modulation on pharmacological or psychological treatments has never been investigated.MethodsOne hundred sixty MDD patients were partially randomized to either inter-personal counseling (IPC) or antidepressants. The primary outcome was remission at week 8. Five serotonergic polymorphisms were investigated (COMT rs4680, HTR1A rs6295, HTR2A rs2224721, HTR2A rs7997012 and SLC6A4 rs421417).ResultsIPC (n=43) and antidepressant (n=117) treated patients did not show any difference in remission rates at week 8 (corrected for baseline severity, age and center). None of the studied gene variants impacted on response and remission rates at week 8 neither in the IPC nor in the antidepressant group. An analysis of the whole sample showed a trend of association between rs7997012 AA genotype and a better treatment outcome.ConclusionOur study confirms that IPC is an effective psychological intervention comparable to antidepressants in mild-moderate MDD. Polymorphisms related to the serotonin system did not exert a major effect on clinical outcomes in none of the treatment groups.

Genome-wide association study of antidepressant treatment-emergent suicidal ideation.

Emergence of suicidal ideation (TESI) during treatment with antidepressants in major depression led to a black box warning. We performed a genome-wide association study to identify genetic markers, which increase the risk for this serious side effect. TESI was evaluated in depressed in-patients (N=397) and defined by an emergence of suicidal thoughts during hospitalization without suicidal thoughts at admission using the suicide item (3) of the Hamilton Depression Rating Scale. Genotype distribution of 405.383 single-nucleotide polymorphisms (SNPs) in patients with TESI (N=32/8.1%) was compared to patients without increase in suicidal ideation (N=329/82.9%) and to a subgroup never reported suicidal ideation (N=79/19.9%). Top results were analyzed in an independent sample (N=501). None variant reached genome-wide significance, the best associated SNP was rs1630535 (p-value=1.3 × 10(-7)). The top 79 SNPs could be analyzed in an independent sample, and 14 variants showed nominal significant association with the same risk allele in the replication sample. A discriminant analysis classifying patients using these 79 SNPs revealed a 91% probability to classify TESI vs non-TESI cases correctly in the replication sample. Although our data need to be interpreted carefully owing to the small numbers in both cohorts, they suggest that a combination of genetic markers might indeed be used to identify patients at risk for TESI.

No influence of PTGS2 polymorphisms on response and remission to antidepressants in major depression

In the present study, aimed at investigating whether a set of single nucleotide polymorphisms (SNPs) within PTGS2 gene (rs4648276, rs2066826 and rs689466) could be associated with antidepressant response, remission and treatment resistance in a sample of major depression patients, we did not find evidence supporting any of such associations.

PMH54 USE OF THE ANALYTIC HIERARCHY PROCESS TO PRIORITIZE PATIENT-RELEVANT ENDPOINTS OF ANTIDEPRESSANT TREATMENT

OBJECTIVES: In deciding about coverage of new medical technology, multiple clinical outcomes are used to support reimbursement claims. Neither the real world value nor the relevance of these outcome measures for patients is systematically assessed. Hence, there is growing interest in the use of patient-reported outcome measures. Multi-criteria decision analysis, like the analytic hierarchy process (AHP), is a technique to elicit patient preferences. In the present study we used AHP to prioritize patient relevant endpoints related to the use of antidepressants in major depression. METHODS: Patient relevant endpoints of treatment (remission of depression, response to treatment, no relapse, serious adverse events, adverse events, social function, anxiety, pain, cognitive function) were prioritized using pairwise comparisons of these outcomes. In two separate groups, twelve patients and seven experts judged on a 9 point scale the relative importance of pairs of two outcome measures. The geometric mean of these judgments was used to derive weighting factors for the outcome measures (scale 0–1). RESULTS: Of all outcome measures, patients rated response to treatment highest (0.32), while experts rated remission of depression highest (0.48). Adverse events were all rated lowest by patients as well as by experts, and diseasespecific quality of life domains such as social function (0.11 & 0.09), anxiety (0.12 & 0.05) and cognitive function (0.13 & 0.06) were rated in between. CONCLUSIONS: The most important outcome measures according to the patients are, in order of decreasing importance: response, cognitive function, no anxiety, social function, no relapse, no adverse events, and remission. The AHP appears to be suitable in gaining an overview of the importance of patient relevant outcome measures. An additional advantage of AHP is that the group discussions offer insight in the question why the endpoints are important.

Brain effects of antidepressants in major depression: A meta-analysis of emotional processing studies

BackgroundA consistent brain activity pattern has been identified in major depression across many resting positron emission tomography (PET) studies. This dysfunctional pattern seems to be normalized by antidepressant treatment. The aim of this meta-analysis was to identify more clearly the pattern associated with clinical improvement of depression following an antidepressant drug treatment, in emotional activation studies using functional magnetic resonance imaging (fMRI). MethodsA quantitative Activation Likelihood Estimation (ALE) meta-analysis was performed across 9 emotional activation fMRI and PET studies (126 patients) using the Activation Likelihood Estimation technique. ResultsFollowing the antidepressant drug treatment, the activation of dorsolateral, dorsomedial and ventrolateral prefrontal cortices was increased whereas the activation of the amygdala, hippocampus, parahippocampal region, ventral anterior cingulate cortex, orbitofrontal cortex, and insula was decreased. Additionally, there was a decreased activation in the anterior (BA 32) and posterior cingulate cortices, as well as in the precuneus and inferior parietal lobule, which could reflect a restored deactivation of the default mode network. LimitationsThe small number of emotional activation studies, using heterogeneous tasks, included in the ALE analysis. ConclusionsThe activation of several brain regions involved in major depression, in response to emotional stimuli, was normalized after antidepressant treatment. To refine our knowledge of antidepressants' effect on the neural bases of emotional processing in major depression, neuroimaging studies should use consistent emotional tasks related to depressive symptoms and that involve the default mode network, such as self-referential processing tasks.

S56-03 IPT in physical diseases. The diabetes mellitus case

Introduction:Prevalence of Major Depression in populations with physical diseases as Diabetes Mellitus is twice or more than in general population. As IPT framework concerns relationships, communication skills and problem solving, all significant in adjustment to chronic disease, it is a potential treatment indication in such a clinical situation. Some IPT work has been done in HIV populations.Objectives:Treatment results with IPT or antidepressants in Major Depression in Diabetes Mellitus Type 2. Secondary outcomes are differences in attachment, diabetes psychological adjustment and metabolic control.Method:20 adult outpatients with type 2 Diabetes and Major Depression with no other comorbidity (except chronic diabetes complications) randomized to usual treatment (SSRI and consultation or IPT. Combined treatment added if patient wasn't 25% better from basal MADRS score at 6th week. Metabolic control obtained with HbA1c.Results:Patients distribution:IPT-7; Usual-7; Combo-2; Dropouts: Usual-3; Combo-1. Patients characteristics: 54,55±6,75 years aged, 85% female gender, 6,25±2,99 years education, HbA1c 8,94%±2,31. Paired samples test comparing basal values and at 6 months: usual treatment and IPT both efficacious in reducing MADRS scores by 50% (p< .01); usual treatment patients with better diabetes psychological adjustment and anxious attachment lowering (both p< .05); metabolic control better with IPT, but not significant (p=0,1).Conclusion:These are preliminary results with a small sample, but pointing towards the usefulness of IPT in depressive type 2 diabetic patients. Discussion will pay particular attention on benefits of psychological change related to Diabetes and to personal life with aid from clinical examples.

Heat-shock protein-70 genes and response to antidepressants in major depression

In the search of predictors of antidepressant efficacy, much interest has recently focused on pro-inflammatory proteins, as they were found to be elevated during major depressives states and decreased by antidepressant drugs. In the present paper we investigated the role of the genes coding for heat-shock-70 family proteins, recently hypothesized to be activated by antidepressants and thus mediate the reduction of pro-inflammatory cytosines. One hundred and forty two hospitalised patients, affected by major depression and treated with antidepressants drugs for a major depressive episode were evaluated for depressive severity at the baseline and at the discharge and genotyped for five SNPs within the genes HSPA1L, HSPA1A and HSPA1B. Markers were not individually associated with symptom severity after treatment. Instead, we found a three markers haplotype, including SNPs within HSPA1L and HSPA1A, associated with a poorer response to antidepressant treatment ( p = 0.005). Single markers as well as haplotypes were not associated with other clinical features. In conclusion, genetic variants within the genes coding for HSP-70 family proteins may affect the action of antidepressants and thus their therapeutic efficacy.

Shortened onset of action of antidepressants in major depression using acetylsalicylic acid augmentation: a pilot open-label study

Based on our preclinical data showing a potential accelerating effect of acetylsalicylic acid (ASA) in combination with fluoxetine in an animal model of depression, we examined the effect of ASA augmentation therapy on selective reuptake inhibitors (SSRI) in major depressed non-responder patients. Twenty-four non-responder patients having received at least 4 weeks of an adequate SSRI treatment were included in a pilot open-label study. Participants were treated openly during 4 weeks with 160 mg/day ASA in addition to their current antidepressant treatment. The combination SSRI-ASA was associated with a response rate of 52.4%. Remission was achieved in 43% of the total sample and 82% of the responder sample. In the responder group, a significant improvement was observed within week 1 (mean Hamilton Depression Rating Scale-21 items at day 0=29.3+/-4.5, at day 7=14.0+/-4.1; P<0.0001) and remained sustained until day 28. Despite limitations due to the open nature of this study, our preliminary results confirm our preclinical findings and are in favour of an accelerating effect of ASA in combination with SSRIs in the treatment of major depression. Potential physiological and biochemical mechanisms may involve an anti-inflammatory and/or neurotrophic effect.

WHO RECEIVES ANTIDEPRESSANTS AND WHAT IMPACT DO THEY HAVE? AN ACUTE-CARE STUDY

The purpose of this study was to examine characteristics associated with prescribing antidepressants in major depression and the utility of such antidepressants in an acute-care, inpatient setting. Demographic and clinical (self-report and clinician-rated scales) were obtained for 111 inpatients diagnosed with major depression. Three comparison sets were made: (1) all patients prescribed antidepressants versus those who were not; (2) those in the top quartile for length of stay (LOS) versus those in the bottom quartile; and (3) patients discharged in less than one week who were prescribed versus not prescribed, antidepressants. Overall, minimal differences were found in the three comparison sets. Those prescribed antidepressants had higher admission BDI scores, longer LOS, more previous episodes, higher education levels, and were more likely to be admitted voluntarily. At admission, there were no clear predictors of LOS. Regardless of differences between groups at admission or discharge (antidepressant versus no antidepressant, short versus long LOS), no differences were found in the length of time before patients were readmitted. These findings suggest that the traditional practice of avoiding immediate medication at hospitalization appears to have some validity.