Psychotherapy effectiveness for major depression: a randomized trial in a Finnish community.

BACKGROUND: The purpose of this study is to assess the relative effectiveness of Interpersonal Psychotherapy (IPT), Psychoeducative Group Therapy (PeGT), and treatment as usual (TAU) for patients with Major Depressive Disorder (MDD) in municipal psychiatric secondary care in one Finnish region. METHODS: All adult patients (N = 1515) with MDD symptoms referred to secondary care in 2004-2006 were screened. Eligible, consenting patients were assigned randomly to 10-week IPT (N = 46), PeGT (N = 42), or TAU (N = 46) treatment arms. Antidepressant pharmacotherapy among study participants was evaluated. The Hamilton Depression Rating scale (HAM-D) was the primary outcome measure. Assessment occurred at 1, 5, 3, 6, and 12 months. Actual amount of therapists' labor was also evaluated. All statistical analyses were performed with R software. RESULTS: All three treatment cells showed marked improvement at 12-month follow-up. At 3 months, 42 % in IPT, 61 % in PeGT, and 42 % in TAU showed a mean ≥50 % in HAM-D improvement; after 12 months, these values were 61 %, 76 %, and 68 %. Concomitant medication and limited sample size minimized between-treatment differences. Statistically significant differences emerged only between PeGT and TAU favoring PeGT. Secondary outcome measures (CGI-s and SOFAS) showed parallel results. CONCLUSION: All three treatments notably benefited highly comorbid MDD patients in a public sector secondary care unit. TRIAL REGISTRATION: ClinicalTrials.gov NCT02314767 (09.12.2014).

Efficacy of extended release quetiapine fumarate monotherapy in elderly patients with major depressive disorder: secondary analyses in subgroups of patients according to baseline anxiety, sleep disturbance, and pain levels.

This study evaluated extended release quetiapine fumarate (quetiapine XR) monotherapy in elderly patients with major depressive disorder (MDD) according to baseline levels of anxiety, sleep disturbance, and pain. Post-hoc analyses of data from an 11-week (9-week randomized-treatment, 2-week post-treatment phase), double-blind, placebo-controlled study of quetiapine XR (50-300 mg/day) monotherapy in elderly (≥66 years) patients (n=338) with MDD were carried out. Outcomes included randomization to week 9 change in Montgomery Åsberg Depression Rating Scale (MADRS) score and week 9 response (≥50% MADRS score reduction) rates. Post-hoc analyses were carried out to assess subgroups of patients with MDD according to baseline levels in terms of the following: higher or lower anxiety (Hamilton Rating Scale for Anxiety total score≥20 or < 20, respectively); high or low sleep disturbance [Hamilton Rating Scale for Depression sleep disturbance factor (items 4+5+6) score≥5 or <5, respectively]; and pain visual analog scale total score 40 mm or higher or less than 40 mm. At week 9, quetiapine XR reduced the MADRS total score compared with placebo in the higher anxiety (least squares mean change -17.8 vs. -8.5; P<0.001) and lower anxiety (-14.8 vs. -8.8; P<0.001) subgroups. MADRS total score was also reduced with quetiapine XR compared with placebo in the high (-17.6 vs. -8.7; P<0.001) and low (-14.4 vs. -9.2; P<0.001) sleep disturbance subgroups, as well as in the pain visual analog scale subgroups [≥40 mm (-16.6 vs. -8.9; P<0.001) and <40 mm (-15.7 vs. -8.7; P<0.001)]. Quetiapine XR response rates were higher than those of placebo in all subgroups analyzed. In this study, quetiapine XR (50-300 mg/day) monotherapy was shown to be effective against depressive symptoms in elderly patients with MDD, irrespective of baseline levels of anxiety, sleep disturbance, and pain.

Randomized, double-blind study of the efficacy and tolerability of extended release quetiapine fumarate (quetiapine XR) monotherapy in elderly patients with major depressive disorder.

OBJECTIVES: This study assessed the efficacy and tolerability of once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy in elderly patients with major depressive disorder (MDD). DESIGN: An 11-week (9-week randomized; 2-week posttreatment phase), double-blind, placebo-controlled, Phase III study (D1448C00014). SETTING: A total of 53 centers in Argentina, Estonia, Finland, Russia, Ukraine, and the United States. PARTICIPANTS: A total of 338 patients (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of MDD, age ≥66 years, Hamilton Rating Scale for Depression [HAM-D] total score ≥22, HAM-D Item 1 [depressed mood] score ≥2) were randomized (mean age: 71.3 years). INTERVENTION: Patients were randomized to quetiapine XR (n = 166; flexible-dosing 50-300 mg/day) or placebo (n = 172). MEASUREMENTS: Primary outcome was Montgomery Åsberg Depression Rating Scale (MADRS) total score change from randomization at Week 9. RESULTS: At Week 9, quetiapine XR (least squares [LS] means: -16.33, standard error [SE]: 0.95; mean change: -16.0, standard deviation [SD]: 9.3) significantly reduced MADRS total score from randomization versus placebo (LS means [SE]: -8.79 [0.94]; mean [SD]: -9.0 [9.9]); significant improvements were also seen at Week 1 (LS means [SE]: -4.65 [0.53] versus -2.56 [0.53], respectively; mean [SD]: -4.3 [5.1] versus -2.4 [3.7], respectively). At Week 9, secondary outcome variables significantly improved with quetiapine XR versus placebo, including MADRS response (≥50% reduction in total score); MADRS remission (total score ≤8); HAM-D total, HAM-A total, HAM-A psychic and somatic cluster, and Clinical Global Impressions-Severity of Illness (CGI-S) total scores; proportion of patients with CGI-Improvement score of 2 or less; Q-LES-Q-SF% maximum total, Pittsburgh Sleep Quality Index global, and pain Visual Analog Scale scores. Common adverse events (>10% patients with quetiapine XR) were somnolence, headache, dry mouth, and dizziness. CONCLUSION: In elderly patients with MDD, quetiapine XR monotherapy (50-300 mg/day, flexibly dosed) is effective at improving depressive symptoms, with symptom improvement observed as early as Week 1. Overall tolerability and safety were consistent with the known profile of quetiapine.

Interleukin-1 beta gene polymorphism and its interactions with neuregulin-1 gene polymorphism are associated with schizophrenia.

Interleukin-1beta (IL-1beta) and neuregulin-1 (NRG-1) have an important role in development of the central nervous system. Several recent studies suggest that their genetic polymorphisms are associated with schizophrenia. We studied the effects of the IL-1beta gene (IL-1B) -511 and NRG-1 SNP8NRG221533 polymorphisms and their interactions on the risk and age of onset of schizophrenia in 113 Finnish schizophrenic patients and 393 healthy controls. The allele and genotype frequencies of IL-1B and NRG-1 did not differ between schizophrenic patients and healthy controls, but the risk of schizophrenia was more than 10 times higher (odds ratio 10.20, 95% CI 2.53-41.09, p = 0.001) among subjects with the IL-1B 2.2, NRG-1 CC genotypes compared to subjects with the IL-1B 2.2, NRG-1 T-allele carriage. There was also a trend for an association between the interaction between IL-1B and NRG-1 polymorphisms and the age at onset of schizophrenia (chi(2) = 2.80; df = 1; p = 0.09, log rank test). IL-1B-511 allele 1 homozygotes had a significantly higher age of onset than allele 2 carriers (mean age of onset 25.9 +/- 7.7 and 22.7 +/- 5.4 years, t-test: t = 2.46; p = 0.032). Our results suggest that there is an interaction between the IL-1B and NRG-1 genes in schizophrenia. In addition, the IL-1B-511 polymorphism seems to be associated with the age at onset of schizophrenia.

Quality of treatment and disability compensation in depression: comparison of 2 nationally representative samples with a 10-year interval in Finland.

OBJECTIVE: Depressive disorders cause substantial work impairment that can lead to disability compensation. The authors compared treatment received for depression preceding disability pension between 2 nationally representative samples with a 10-year interval. METHOD: The medical statements for 2 random samples drawn from the Finnish national disability pension registers, representing populations granted a disability pension for DSM-III-R major depression during a 12-month period from October 1993 through September 1994 (N = 277) and for ICD-10 depressive disorders (F32-F33) from October 2003 through September 2004 (N = 265) were examined. The proportions of persons receiving weekly psychotherapy, antidepressants, adequate antidepressant dosage, sequential antidepressant trials, lithium augmentation, and electroconvulsive therapy (ECT) were compared. RESULTS: No significant differences emerged between the 2 samples, except for the adequacy of antidepressant dosage. Few subjects in either of the samples (8.7% for 1993-1994 vs. 10.6% for 2003-2004, p = .45) had received weekly psychotherapy. Most had received antidepressants (87.4% vs. 85.6%, p = .55) with increasingly adequate dosage (75.6% vs. 85.0%, p = .02), but only a minority had received sequential antidepressant trials (39.5% vs. 44.5%, p = .24). Lithium augmentation and ECT were rare (1.1% vs. 1.5%, p = .66 and 4.0% vs. 1.5%, p = .08, respectively). Even in 2003-2004, over half of the subjects were granted a disability pension without sequential antidepressant trials. CONCLUSION: This nationally representative study indicates that, despite an increased antidepressant use and improved practice guidelines for depression, a considerable proportion of the people granted long-term compensation for depression seem to be suboptimally treated. Given the enormous costs of the disability, attention to the quality of treatment provided for depression is warranted before long-term disability compensations are granted.

Catechol-O-methyltransferase val108/158met genotype and response to antipsychotic medication in schizophrenia.

Catechol-O-methyltransferase (COMT) gene has been investigated as a possible candidate gene in schizophrenia. The most studied polymorphism has been the functional val108/158met polymorphism of this COMT gene. There is also some evidence that this polymorphism could be related to drug response to antipsychotics in schizophrenia. COMT enzyme inactivates dopamine and noradrenaline. Based mainly on the original dopamine theory of schizophrenia, our primary hypothesis was that the maintenance dose of antipsychotics would be higher in patients with the low activity COMT genotype. In this study we evaluated the current daily dosage of antipsychotics in 180 patients with schizophrenia in connection with the COMT genotype. We could not demonstrate any clearly significant effect of this particular COMT genotype in relation to the daily maintenance dosages of antipsychotics in patients with schizophrenia.

Epidermal growth factor a61g polymorphism is associated with the age of onset of schizophrenia in male patients.

There is evidence to suggest that dysfunction of dopaminergic neurotransmission in the central nervous system (CNS) plays a role in the etiopathology of schizophrenia. Epidermal growth factor (EGF) gene polymorphism has an impact on EGF production in mononuclear cells, and EGF seems to affect the development of midbrain dopaminergic neurons. The few studies concerning EGF gene polymorphism and schizophrenia have yielded contradictory results. Our aim was to investigate whether EGF gene A61G polymorphism predisposes to schizophrenia, and this polymorphism was therefore studied in 149 schizophrenic patients and in 94 healthy controls using 5' nucleotidase assay (TaqMan). As far as EGF A61G polymorphism was concerned, we detected no significant differences in the allele and genotype frequencies between the patients and the controls. However, the G/G genotype was significantly associated with an earlier age of onset of schizophrenic psychosis in male subjects (P=0.005) as well as in the entire population, but not in female patients (P=0.008 and 0.46, respectively). The average age (+/-SD) of onset of schizophrenia was 20.1+/-3.9 years in male EGF A61G G/G homozygotes and 23.7+/-6.6 (P=0.02) years in other genotypes. In conclusion, EGF gene polymorphism was not associated with the risk of schizophrenia. However, the EGF G/G genotype, which has been suggested to involve abundant production of EGF, was associated with early onset of schizophrenia in male patients.

Association between the C957T polymorphism of the dopamine D2 receptor gene and schizophrenia.

The aim of this study was to investigate the relationship between the functional C957T single-nucleotide polymorphism of the dopamine D2 receptor (DRD2) gene and the risk for schizophrenia. We therefore conducted a case-control association study of 188 Finnish schizophrenia patients meeting the DSM-IV criteria and 384 healthy controls. The 5' nuclease assay (TaqMan) was used to determine genotypes. A greater proportion of patients with schizophrenia than healthy controls were C-allele carriers (odds ratio 1.5, 95% confidence interval (CI) 1.0-2.3, P=0.05). Our results are in agreement with an earlier association study suggesting that the C957T C-allele plays a role in the genetic vulnerability for schizophrenia and support the involvement of the DRD2 gene in schizophrenia pathogenesis.

Tumor necrosis factor-alpha --G308A polymorphism in schizophrenia in a Finnish population.

Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine with functions in nerve cell growth, differentiation, and apoptosis. There are several studies showing that a TNF-alpha--G308A promoter polymorphism, which possibly affects TNF-alpha transcription, is associated with schizophrenia, although negative results also exist. Our aim was to investigate the relationship between the TNF-alpha --G308A promoter polymorphism, the risk of schizophrenia, and the age of onset of schizophrenia, and the TNF-alpha -G308A polymorphism was therefore studied in 149 southern Finnish patients with a DSM-IV diagnosis of schizophrenia and in 393 healthy controls. The allele and genotype frequencies did not differ significantly between the patient and control groups (P=0.10 and 0.12, respectively), but the frequency of G/G homozygotes was statistically significantly higher in male patients than in male controls (chi(2)=5.03, d.f.=1, P=0.025) with an odds ratio of 2.00 (95% confidence interval: 1.08--3.70). No such difference was seen in female patients (P=0.79) or in the whole study group (P=0.064). The age of onset of schizophrenia did not differ significantly between the different TNF-alpha genotypes (ANOVA: F=0.45, P=0.64). In conclusion, we did not find a clear association between the TNF-alpha --G308A polymorphism and schizophrenia in the whole study group. However, TNF-alpha --G308A G/G homozygosity was modestly associated with schizophrenia in male patients.

REM sleep and prolactin in patients with non-affective psychoses.

Reduced REM latency is a common polysomnographic finding in patients with schizophrenia. This has been attributed to cholinergic hyperactivity secondary to increased dopaminergic tone. We studied polysomnographic sleep recordings, and morning serum prolactin levels as a measure of dopaminergic tone in 17 drug-free patients suffering from non-affective psychoses, hypothesizing that REM-latency and prolactin would correlate. A clear-cut positive correlation between prolactin and REM latency was found, as well as a negative correlation between prolactin and REM sleep. The findings may be explained by dopaminergic and secondary hypercholinergic and/or serotonergic mechanisms responsible for the regulation of REM sleep and the secretion of prolactin.

Right unilateral and bifrontal electroconvulsive therapy in the treatment of depression: a preliminary study.

The short-term outcome of electroconvulsive therapy (ECT) was studied in 24 patients with a current major depressive episode (DSM-IV). Patients were randomized to high dose (400% above the seizure threshold) right unilateral (RUL) ECT, to moderate dose (150% above seizure threshold) RUL ECT, and to low dose (just above seizure threshold) bifrontal (BF) ECT. Primary outcome measures included number of treatments, Hamilton Depression Rating Scale score, and Mini-Mental State Examination score. High dose RUL ECT was associated with a significantly faster response to treatment than low dose BF ECT. Moreover, there was a tendency to a higher response rate with high dose RUL ECT compared with either moderate dose RUL ECT or BF ECT.

Differential response to right unilateral ECT in depressed patients: impact of comorbidity and severity of illness [ISRCTN39974945].

BACKGROUND: Recent electroconvulsive therapy (ECT) efficacy studies of right unilateral (RUL) ECT may not apply to real life clinics with a wide range of patients with major depressive episodes. METHODS: The study included two groups of patients. In addition to a homogeneous group of patients with major depression according to DSM-IV criteria with severity of the major depressive episode > 16 scores on 17-item Hamilton Rating Scale for Depression (HDRS) (Group 1, n = 16), we included a heterogeneous group of patients with less severe major depressive episodes or with a variety of comorbid conditions (Group 2, n = 24). We randomly assigned the patients to an RUL ECT treatment dosed at 5 or 2.5 times seizure threshold with an intent-to-treat design. The outcomes measured blindly were HDRS, number of treatments, and Mini-Mental State Examination (MMSE). The patients were considered to have responded to treatment if the improvement in HDRS score was at least 60% and they had a total score of less than ten. RESULTS: The Group 2 patients responded poorer (8% vs. 63%), and had more often simultaneous worsening in their MMSE scores than Group 1 patients. The differences in the outcomes between the two different doses of RUL ECT treatment were not statistically significant. CONCLUSIONS: ECT effectiveness seems to be lower in real-life heterogeneous patient groups than in homogeneous patient samples used in experimental efficacy trials.

Impaired temporal lobe processing of preattentive auditory discrimination in schizophrenia.

Feature-specific stimulus discrimination related to short-term auditory sensory memory can be studied electrophysiologically using a specific event-related potential (ERP) component termed mismatch negativity (MMN), which is generated in the auditory cortex, indexing automatic comparison of the existing memory trace to incoming novel stimuli. Previous results with electroencephalography (EEG) and magnetoencephalography (MEG) suggest that schizophrenia patients have attenuated MMN response and that preattentive auditory processing preceding MMN appears to be functionally asymmetric in schizophrenia. Here we studied parallel MMN activity of the hemispheres using a whole-head MEG by presenting stimulus blocks consisting of frequent standard and infrequent deviant tones to 15 schizophrenia patients and 19 healthy control subjects. Auditory evoked fields (AEFs) were recorded simultaneously over both auditory cortices. The equivalent current dipole (ECD) modeling revealed that patients had significant MMNm reduction (magnetic counterpart of MMN) in both temporal lobes. In addition, patients had significantly delayed MMNm in the left but not in the right hemisphere to ipsilateral auditory stimuli. These results suggest that patients with schizophrenia have impaired auditory processing in the temporal lobes underlying preattentive stimulus discrimination that is also selectively delayed in the left hemisphere.