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Aims: Literature data show that one third of patients discontinue antidepressant therapy within the first month of treatment. The aim of this study was to evaluate whether paroxetine liquid solution 10 mg/ml may influence adherence inpatients receiving long-term treatment., Methods: 71 subjects affected by mood disorders or panic disorder were monitored for six months. The study sample was divided into two groups: controls (n=33) maintained their own therapy with paroxetine tablets; 38 patients maintained the same dosage of paroxetine, but shifted to liquid formulation 10 mg/ml. Compliance and general wellness were evaluated with the Medication Adherence Rating Scale (MARS) and the World Health Organization Quality of Life questionnaire (WhoQol). Data were analyzed using analysis of variance (ANOVA) and multivariate analysis of covariance (MANCOVA)., Results: Significant differences were found in MARS scores: patients on oral solution 10 mg/ml showed an improvement of compliance month by month. In addition, age, formulation and quality of life had a significant impacton patient compliance. Significant correlations were found between MARS and quality of life. A specific paroxetine formulation could be a variable able to influence adherence to psychopharmacological treatment. The same consideration can be made for quality of life, sex and age that showed a trend towards improved adherence when compared with controls. Inparticular, the WhoQol subscale analysis of delta scores showed a significant difference in self-perception of quality of life inpatients treated with paroxetine either in tablet or drop formulation., Discussion: Formulation in drops 10 mg/ml is equally effective to tablets, but it may allow patients having a higher cognition and control on drug assumption.

Background: Transcranial Magnetic Stimulation (TMS) is an effective technique in the treatment of depression, specifically in drug-resistant patients. However, there is little data available on the influence of genetic variables on TMS response., Methods: We analyzed the role of three genetic polymorphisms that affected the antidepressant response: serotonin transporter promoter region (SERTPR) polymorphism, 5-HT(1A) serotonergic receptor promoter region polymorphism (rs6295), and the coding region of COMT gene polymorphism (rs4680). Ninety patients with a major depressive drug-resistant episode due to a Major Depressive Disorder or to a Bipolar Disorder were included in our study. Patients underwent high frequency TMS, focused on the left prefrontal cortex, for 2 weeks. At study completion, the response rate was 45.5%. Effects of gene polymorphisms on clinical improvement were analyzed with an analysis of variance with each gene (SERTPR, 5-HT(1A) , and COMT) as factors and the Hamilton Rating Scale for Depression variation from baseline to the end of the treatment as a dependent variable., Results: We found a significant model in which three factors were not significant (diagnosis, COMT, and SERTPR), whereas factor 5-HT(1A) showed a significant influence on the outcome, with patients with C/C genotype showing a greater improvement than G/G and C/G and no difference between G/G and C/G., Conclusion: According to our data, 5-HT(1A) polymorphism may play a role in influencing TMS response. The effect of COMT and SERTPR did not reach statistical significance. The analysis of these and other candidate genes in larger samples could help explain genetic influence on TMS response., (© 2011 Wiley-Liss, Inc.)

Background: We have investigated the efficacy of high-frequency left (HFL) versus low-frequency right (LFR) repetitive transcranial magnetic stimulation (rTMS) in depression, focusing on specific symptoms as possible predictors of outcome for these two different types of stimulation., Method: Seventy-four outpatients with a major depressive episode treated with an adequate antidepressant dosage for at least 4 weeks were included in our study and randomly assigned to two different groups: HFL or LFR rTMS. The Hamilton Rating Scale for Depression (HAM-D) items were pooled into 6 factors to evaluate specific symptoms as possible predictors of response., Results: Twenty-one out of 32 patients (65.6%) and 24 out of 42 patients (57.1%) were responders in the HFL and LFR groups, respectively. No significant difference in response rate was observed. Considering the whole sample, we found an inverse correlation between activity and HAM-D score reduction and a significant positive relation between somatic anxiety and outcome. An inverse correlation between psychic anxiety and HAM-D score reduction emerged considering the HFL group. In the LFR group, there was a significant negative relationship between baseline activity and the outcome., Conclusion: These findings support the hypothesis that LFR rTMS could be as effective as HFL rTMS and more suitable for patients with a higher anxiety degree, particularly in bipolar patients., (Copyright 2010 S. Karger AG, Basel.)

The 5-HT2A receptor is a key modulator of the serotonin pathway. We previously observed a marginal association between 5-HT2A gene variants and antidepressant efficacy in Japanese and Italian population but in the opposite direction. In the present report, we hypothesize that discrepant findings on 5-HT2A gene variants could be due to both the effect of ethnicity and a possible specific effect on some symptom improvement. The sample comprised 203 patients affected by mood disorders and treated for major depression with paroxetine or fluvoxamine. The total depressive scores for all patients were analyzed in previous reports, but symptomatologic clusters were not examined previously. The 21-item Hamilton Rating Scale for Depression (HAM-D) was administered to evaluate depressive symptoms at baseline and bi-weekly over 6 weeks of treatment. All patients were genotyped for the 5-HT2A T102C polymorphism. Compared with patients with the 5-HT2A T and C variants, in the Japanese sample T allele carriers showed selective and slower score reductions than C allele carriers in delusion and activity symptoms; on the other hand, in the Italian sample, C allele carriers showed a slower and selective score reduction compared with T allele carriers in Somatic anxiety, while they did not differ from other patients on the other scores. Despite the limitations of the small sample size and modest significance levels, these findings suggest that response to SSRIs is not a unitary phenomenon and discrepant findings across ethnic groups may be due to differential effects of gene variants.

It is often stated that depressive phenomenology and prognosis differ between elderly and younger depressed patients, in the direction of more severe symptoms and a poorer outcome in elderly individuals. However, studies addressing the topic remain largely inconclusive, and it has been suggested that potential biases connected with age may have confounded previous assessments. In this work we evaluated a sample of 93 elderly depressed individuals (>60 years) and 186 younger patients. All patients were assessed with the 21-item Hamilton Depression Rating Scale at intake and prospectively followed for 6 weeks during treatment with antidepressants. A number of clinical and demographic features were taken into account to investigate depressive phenomenology and outcome in late-life depression. We found that the high likelihood of medical disorders in elderly patients explained the more severe depressive symptomatology observed in this population. However, independently from physical problems, recovery was slightly slower in elderly compared with younger individuals. Finally, patients who developed their first lifetime episode late in life (>60 years) showed a form of symptomatology similar to that in elderly patients with an earlier onset, but they showed a more positive outcome. In conclusion, the present work suggests that depression in old age is similar to depression in other ages, except for a slightly slower response to pharmacotherapy. Minor health problems increase the severity of depression, but they do not interfere crucially with the efficacy of antidepressant treatment. Finally, late-onset depression is associated with a positive outcome.

Background/objective: Repetitive transcranial magnetic stimulation (rTMS) has been mainly studied as adjunctive treatment for drug-resistant patients. We assessed the effectiveness of rTMS started concomitantly with antidepressant medications in non-drug-resistant major depressive disorder patients. We also evaluated if, among the 3 antidepressants administered, one had a better synergy with rTMS., Method: In this 5-week, double-blind, randomized, sham-controlled study, we recruited 99 inpatients suffering from a major depressive episode (DSM-IV criteria). They were randomly assigned to receive venlafaxine, sertraline, or escitalopram in combination with a 2-week period of sham or active 15-Hz rTMS on the left dorso-lateral prefrontal cortex. Data were gathered from February 2004 to June 2005., Results: The active rTMS group showed a significantly faster reduction in Hamilton Rating Scale for Depression (HAM-D) scores compared with the sham group (p = .0029). The response and remission rates were significantly greater in the active rTMS group after the stimulation period (p = .002 and p = .003, respectively), but not at the endpoint. We found no significant difference in HAM-D score reduction among the 3 drugs administered, either in the active or in the sham group., Conclusion: These findings support the efficacy of rTMS in hastening the response to antidepressant drugs in patients with major depressive disorder. The effect of rTMS seems to be unaffected by the specific concomitantly administered drug.

This 5-week, randomized, double-blind, placebo-controlled trial investigated the efficacy and tolerability of high frequency repetitive transcranial magnetic stimulation (rTMS) directed to the left prefrontal cortex in drug-resistant depressed patients. Fifty-four patients were randomly assigned to receive 10 daily applications of either real or sham rTMS. Subjects assigned to receive active stimulation were divided into two further subgroups according to the intensity of stimulation: 80% vs. 100% of motor threshold (MT). At study completion, the response rates were 61.1% (n=11), 27.8% (n=5) and 6.2% (n=1) for the 100% MT group, 80% MT group and sham group, respectively. A significant difference (Pearson chi(2) test) was found between the 100% MT and sham groups, while the 80% MT group did not differ significantly from the sham group. Between the two active groups, a marginally significant difference was observed. Analysis of variance with repeated measures on Hamilton Depression Rating Scale scores revealed a significantly different decrease over time of depressive symptomatology among the three treatment groups. Treatment response appeared to be unrelated to the demographic and clinical characteristics recorded, and on the whole the technique was well tolerated. The results of this double-blind trial showed that rTMS may be a useful and safe adjunctive treatment for drug-resistant depressed patients.

Background: Major depression is a common psychiatric disorder in the elderly population. The efficacy of tricyclic antidepressants is well established, and selective serotonin reuptake inhibitors appear to have a similar effectiveness along with advantages in terms of tolerability and safety. Given the lack of literature data regarding fluvoxamine in the treatment of depressed elderly patients, the aim of the present study was to compare its efficacy and tolerability with those of sertraline in a sample of elderly patients., Methods: Under double-blind conditions, 93 hospitalized patients older than 59 years, who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for a major depressive episode, were randomly assigned to receive sertraline (150 mg daily) or fluvoxamine (200 mg daily) for 7 weeks. The clinical response was defined as a reduction on the Hamilton Rating Scale for Depression score to 8 or below., Results: At study completion, the response rates were 55.6% (25/45) and 71.8% (28/39) for sertraline and fluvoxamine, respectively. No significant difference in final response rates was found between the 2 treatment groups (P = 0.12). A repeated-measures analysis of variance on Hamilton Rating Scale for Depression scores revealed a significantly different decrease of depressive symptoms between the 2 treatment groups, favoring fluvoxamine (P = 0.007). The overall safety profile of sertraline and fluvoxamine was favorable with no differences between the 2 drugs., Conclusion: The results of this double-blind trial show that sertraline and fluvoxamine may be effective compounds in the treatment of elderly depression with the latter showing some advantage in terms of speed of response. These findings warrant further replication in placebo-controlled studies.

Although it is well established that the diagnosis and treatment of depression in the elderly are major health care problems, the relative efficacy of antidepressant treatment in the elderly compared with younger adults has not been definitively established. In this study, we analyzed antidepressant response in 528 nondemented consecutive inpatients affected by a major depressive episode. The sample was divided based on a cut-off of 60 years (< or = 60 n = 354; mean age 46.6 +/- 10.4 years; > 60 n = 174; mean age 66.1 +/- 4.2 years); all the patients were treated with fluvoxamine for at least 6 weeks and they were assessed weekly by using the Hamilton Rating Scale for Depression. Fluvoxamine proved to be effective in our elderly sample, even if antidepressant response was lower in the elderly compared with that of younger subjects (chi2 = 6.27, P = 0.01). Moreover, when compared with younger subjects, the older ones showed significantly slower reduction of depressive symptoms (P = 0.0006). This difference between the 2 age groups was evident since the 2nd week of treatment, and it appeared to be independent of other clinical variables.

The possible association of the dopamine receptor D(2) (Ser 311Cys) and D(4) exon 3 (48 base pair repeat) gene variants with the antidepressant activity of selective serotonin reuptake inhibitors (SSRIs) was investigated in a sample of 364 inpatients affected by a major depressive episode treated with fluvoxamine, 300 mg/day (n=266), or paroxetine, 20-40 mg/day (n=98). The severity of depressive symptoms was assessed weekly with the Hamilton Rating Scale for Depression. Dopamine receptor D(2) (DRD2) and dopamine receptor D(4) (DRD4) allelic variants were determined in each subject by polymerase chain reaction. We observed that DRD2 and DRD4 variants were not associated with response to SSRI treatment. Possible stratification factors, such as sex, diagnosis, presence of psychotic features, depressive symptoms at baseline, paroxetine and fluvoxamine plasma levels, and pindolol augmentation did not significantly influence the observed results. The investigated DRD2 and DRD4 gene variants therefore do not seem to play a major role in the antidepressant activity of SSRIs, at least in the present sample.

Background: It has been recently reported that the short variant of the serotonin transporter (5-HTT) gene-linked functional polymorphic region (5-HTTLPR) influences the antidepressant response to certain selective serotonin reuptake inhibitors. The aim of the present study was to test this finding in a sample of major and bipolar depressives, with or without psychotic features., Methods: One hundred fifty-five inpatients were treated with fluvoxamine 300 mg and either placebo or pindolol in a double-blind design for 6 weeks. The severity of depressive symptoms was weekly assessed with the Hamilton Rating Scale for Depression. Allelic variation of 5-HTTLPR in each subject was determined using a polymerase chain reaction-based technique., Results: 5-HTTLPR short variant was associated with a poor response to fluvoxamine treatment, independently from the recorded clinical variables. More specifically, the diagnosis, the presence of psychotic features, and the severity of depressive symptomatology did not influence this association. Conversely, pindolol augmentation may ameliorate the rate of response in 5-HTTLPR short variant subjects, thus reducing the difference in the response rate among the genotype variants., Conclusions: If confirmed, these results may improve patient care by helping the clinician to individualize treatment according to the patient's genetic 5-HTTLPR pattern.