The impact of depression and somatic symptoms on treatment outcomes in patients with chronic prostatitis/chronic pelvic pain syndrome: a preliminary study in a naturalistic treatment setting.

AIM: The aim of this study was to evaluate the impact of depression and somatic symptoms on treatment outcomes in Korean male patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) attending a routine clinical practice. METHODS: This was a 12-week prospective observational study (n = 80). The Korean version of the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) to measure the severity of CP/CPPS, the Korean version of the Patient Health Questionnaire-9 (PHQ-9) to assess depression, the Korean version of the Patient Health Questionnaire-15 (PHQ-15) to evaluate somatisation and the Korean version of the EuroQol Questionnaire-5 Dimensions (EQ-5D), specifically the EQ-5D utility index and the EQ-5D visual analogue scale (EQ-5D VAS), to assess quality of life, were utilised and given at baseline and week 12. The primary and secondary end-points in this study were changes in the NIH-CPSI total score from baseline to week 12 according to depression and somatisation. RESULTS: The change in NIH-CPSI total score was significantly higher in those without depression than in those with depression (p = 0.003), with a magnitude of difference of 2.8. The responder rate (a ≥ 4 point decrease in NIH-CPSI total score from baseline) was significantly higher in those without depression (42.9%) than in those with depression (17.2%, p = 0.023). However, significant differences were not observed between the two groups in the other outcome measures or in all study outcomes between subjects with or without somatisation. A logistic regression analysis revealed that the presence or absence of depression may be a principal predictor of response to treatment. CONCLUSION: These preliminary results indicate that depression may have a negative impact on treatment outcome and is a likely predictor of response to treatment in patients with CP/CPPS. However, additional studies with adequate power and improved design are necessary to further support the present findings.

Effects of daily low-dose treatment with phosphodiesterase type 5 inhibitor on cognition, depression, somatization and erectile function in patients with erectile dysfunction: a double-blind, placebo-controlled study.

Phosphodiesterase type 5 (PDE5) inhibitors have recently been shown to have cognitive-enhancing effects in animal models and in our previous pilot study. To investigate the efficacy of daily low-dose treatment with a PDE5 inhibitor on cognitive function, depression and somatization in patients with erectile dysfunction (ED), 8-week, double-blind, placebo-controlled study enrolled 60 male patients with ED for ≥ 3 months without cognitive impairment. Forty-nine patients completed the study. Patients were randomized to receive either daily low-dose udenafil 50 mg or placebo for 2 months. The International Index of Erectile Function-5 (IIEF-5), the Korean version of the Mini-Mental State Examination (K-MMSE) for general cognitive function and the Seoul Neuropsychological Screening Battery for comprehensive neuropsychological examination, the Physical Health Questionnaire-9 (PHQ-9) for depression and the Physical Health Questionnaire-15 (PHQ-15) for somatization were administered at baseline and at 2 months. The change in the mean IIEF-5 was significantly higher in the udenafil group than the placebo group (6.08 ± 4.72 vs 2.20 ± 3.50, P=0.008). The changes in the PHQ-9 and PHQ-15 were -2.04 ± 3.14 and -2.17 ± 2.87 in the udenafil group, and 1.20 ± 1.63 and 0.56 ± 2.48 in the placebo group (both, P<0.001). The changes in the K-MMSE and Digit Span Forward were 1.25 ± 1.26 and 0.92 ± 1.02 in the udenafil group, and -0.52 ± 1.19 and -0.24 ± 1.13 in the placebo group (both, P<0.001). However, there were no differences in the other neuropsychological tests. Daily dosing with a PDE5 inhibitor seems to improve cognitive function, depression and somatization, as well as erectile function, in patients with ED.

An open-label, rater-blinded, 8-week trial of bupropion hydrochloride extended-release in patients with major depressive disorder with atypical features.

The present study aimed at investigating the effectiveness and tolerability of -bupropion hydrochloride extended release (XL) in major depressive disorder (MDD) patients with atypical features (AF).51 patients were prescribed bupropion XL for 8 weeks (6 visits: screening, baseline, weeks 1, 2, 4 and 8). The primary efficacy measure was a change of the Structured Interview Guide for the Hamilton Depression Rating Scale-Seasonal Affective Disorder Version (SIGH-SAD) from baseline to endpoint. Secondary efficacy measures included the SIGH-SAD atypical symptoms subscale, Clinical Global Impression-Severity (CGI-S), Sheehan Disability Scale (SDS) and Epworth Sleepiness Questionnaire (ESQ). Response or remission was defined as ≥50% reduction or ≤7 in SIGH-SAD total scores, respectively, at end of treatment.The HAM-D-29 total score reduced by 55.3% from baseline (27.3±6.5) to end of treatment (12.2±6.3) (p<0.001). Atypical symptom subscale scores also reduced by 54.5% from baseline (9.2±3.0) to end of treatment (4.2±2.8) (p<0.001). At the end of treatment, 24.4% (n=10) and 51.2% (n=21) subjects were classified as remitters and responders, respectively. The most frequently reported AEs were headache (13.7%), dry mouth (11.8%), dizziness (9.8%), and dyspepsia (9.8%).Our preliminary study indicates that bupropion XL may be beneficial in the treatment of MDD with atypical features. Adequately powered, randomized, double-blind, placebo-controlled trials are necessary to determine our results.

DAOA variants on diagnosis and response to treatment in patients with major depressive disorder and bipolar disorder.

OBJECTIVE: This study investigated whether selected D-amino acid oxidase activator (DAOA) gene single nucleotide polymorphisms (SNPs; rs3916966, rs3916967, rs2391191, rs3916968, rs7139958, rs9558571, rs778293) are associated with major depressive disorder (MDD) and bipolar disorder (BD), and whether they can predict clinical outcomes in Korean in-patients treated with antidepressants and mood stabilizers, respectively. METHODS: In total, 145 patients with MDD, 132 patients with BD and 170 psychiatrically healthy controls were genotyped for the DAOA SNPs. Baseline and final clinical assessments included the Montgomery-Asberg Depression Rating Scale and Young Mania Rating Scale for patients with MDD and BD, respectively. RESULTS: There was no association between DAOA SNP genotypes or alleles with diagnosis, clinical improvement, response rates or remission rates for MDD and BD. Haplotype analyses found no association with MDD or BD diagnosis or clinical outcomes. CONCLUSIONS: The findings suggest that the DAOA SNPs investigated may not affect MDD or BD phenotype, clinical symptoms or other clinical factors, and are unlikely to be involved in MDD or BD development and treatment outcomes. Given the study's limitations, further investigation should be carried out.

Predictors of response to ziprasidone: results from a 6-week randomized double-blind, placebo-controlled trial for acute depressive mixed state.

INTRODUCTION: The present study is aimed at investigating possible predictors of response to ziprasidone in a sample of patients with mixed depressive state. METHODS: 72 patients were randomized to either ziprasidone or placebo and treated prospectively for 6 weeks. The clinical response and remission were defined with various clinical variables including Montgomery Asberg Depression Rating Scale. Further outcome measures included predictors of remission and other clinical variables over time. RESULTS: None of the variables under investigation were significantly associated with response or remission at 6 weeks (all p-values>0.003, respectively). CONCLUSIONS: Further investigations are warranted due to clear limitations, mostly small sample size and use of concomitant medications.

Available therapies and current management of fibromyalgia: focusing on pharmacological agents.

Fibromyalgia (FM) is a chronic medical condition characterized by physical, psychiatric and psychological symptoms. Widespread pain, fatigue, sleep disturbances, heightened sensitivity, morning stiffness, decreased volition, depressed mood and a history of early abuse are frequently reported by patients with FM. Treatment of fibromyalgia is multidisciplinary, with an emphasis on active patient participation, medications, cognitive-behavioral therapy and physical modalities. No single medication has yet been found to sufficiently control all the symptoms of FM; currently available medication classes include antidepressants, nonsteroidal anti-inflammatory drugs, opioids, sedatives, muscle relaxants, analgesics, hypnotic agents and anticonvulsants. Hence, treatment for patients with FM, including pharmacological and non-pharmacological approaches, should be individualized based on each patient's clinical history, target symptoms and functional impairments. Although nonpharmacological modalities are also frequently used, recent research has focused on identifying more effective pharmacological treatments, particularly antidepressants and anticonvulsants. Furthermore, several new pharmacological agents have been now officially approved for the treatment of patients with FM. Thus, the purpose of this review is to help healthcare professionals make informed decisions about the appropriate use of a number of pharmacological treatments for patients with FM.

Effects of repeated dosing with Udenafil (Zydena) on cognition, somatization and erection in patients with erectile dysfunction: a pilot study.

The PDE5 inhibitors have recently been found to have cognitive-enhancing effects in animal models. To investigate the efficacy of repeated dosing with a PDE5 inhibitor on cognitive function and somatization in patients with erectile dysfunction, 27 patients with erectile dysfunction received udenafil (100 mg) at 3-day intervals for 2 months. The international index of erectile function-5 (IIEF-5), a cognitive battery (the Korean version of mini-mental state examination (K-MMSE), the frontal assessment battery (K-FAB), the Seoul verbal learning test) and a physical health questionnaire-15 (PHQ-15) were performed at baseline and at 2 months, following the administration of udenafil. The patients were divided on the basis of their IIEF-5 score into responders (change>7) and non-responders. The mean IIEF-5 score was significantly increased after treatment (7.92 ± 3.83 to 16.33 ± 4.75, P<0.001). The scores of K-MMSE (27.03 ± 1.58 to 28.07 ± 1.57, P=0.001), K-FAB (13.65 ± 1.96 to 15.41 ± 1.85, P<0.001) and PHQ-15 (18.92 ± 4.96 to 17.63 ± 4.75, P=0.003) were significantly improved after treatment. In addition, the responders (n=16) had more improved cognitive function (r=0.603, P=0.001) and somatization (r=-0.402, P=0.038) than non-responders (n=11). Repeated dosing with a PDE5 inhibitor seems to improve cognitive function and somatization, as well as erectile function in patients with erectile dysfunction.

Impact of the tryptophan hydroxylase 1 gene A218C polymorphism on amygdala activity in response to affective facial stimuli in patients with major depressive disorder.

Tryptophan hydroxylase-1 (TPH1) is the rate-limiting enzyme in serotonin biosynthesis, and allelic variations at the TPH1 locus have been implicated in the pathophysiology of depression. Using 1.5-Tesla functional magnetic resonance imaging, we investigated the possible relationship between TPH1 A218C polymorphism and amygdala response to negative facial stimuli in 26 right-handed female subjects with major depressive disorder (MDD). Genotyping was performed with the polymerase chain reaction. We found a significant association between A allele of the TPH1 A218C polymorphism and neural activations in response to negative facial stimuli. Subjects with the A allele of the TPH1 A218C polymorphism showed greater brain activity in the bilateral amygdala under the sad vs. the neutral condition compared with subjects homozygous for the C allele. Our results suggest that the A218C polymorphism of the TPH1 gene serves as a modulator of amygdala activity in patients with MDD.

Childhood abuse and treatment response in patients with irritable bowel syndrome: a post-hoc analysis of a 12-week, randomized, double-blind, placebo-controlled trial of paroxetine controlled release.

OBJECTIVE: Although irritable bowel syndrome (IBS) is frequently comorbid with childhood trauma, information on the clinical implications of this comorbidity is limited. We investigated whether a history of abuse was associated with response to treatment in a double blind, randomized, placebo controlled trial of paroxetine controlled release (CR) in IBS. METHODS: Seventy-two IBS subjects were randomized to receive paroxetine CR (dose 12.5-50 mg/day) or placebo for 12 weeks. Subject selection was independent of abuse history. Sixty-one subjects completed the Sexual and Physical Abuse Questionnaire about their childhood abuse history. IBS symptoms were recorded using the Interactive Voice Response System (IVRS). Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Perceived Stress Scale (PSS) and Clinical Global Impression (CGI) were also measured. The primary outcome was treatment response defined as > or =25% reduction in composite pain scores (CPS) on the IVRS from randomization to end of treatment. RESULTS: The rate of abuse history was 50.8% (n = 31/61). Baseline demographic clinical characteristics (CPS, BDI, BAI, PSS, CGI scores) were not associated with abuse history. After 12 weeks of treatment, subjects with abuse history showed significantly higher CPS (t = 2.422, P = 0.018) than subjects without a history and less mean change of CPS (t = 3.506, P = 0.001). In a logistic regression analysis, history of abuse did not predict treatment response as measured by > or =25% reduction in CPS (OR = 0.481, CI = 0.164-1.406, P = 0.181), while the drug status (paroxetine CR) was significantly associated with treatment response as defined by a CGI improvement score of 1-2 (OR = 12.121, CI = 2.923-50.271, P = 0.001). Abuse history did not predict CGI-I (Fisher's exact, P = 0.500) improvements during the trial. CONCLUSIONS: History of abuse did not appear to have any significant clinical correlates at baseline and did not predict treatment response. Further studies are needed to confirm whether SSRIs are effective in IBS patients irrespective of their abuse history.

Irritable bowel syndrome in psychiatric perspectives: a comprehensive review.

We comprehensively reviewed the irritable bowel syndrome (IBS) in terms of pathogenesis, psychiatric implications, general management and appropriate role of antidepressants, in particular selective serotonin uptake inhibitors (SSRIs) in the treatment of IBS. English language papers cited in MEDLINE and PychInfo from January 2000 to July 2006 were searched with a combination of the following key words: irritable bowel syndrome, 5-HT, pathogenesis, comorbid, psychiatry, treatment, psychotropic drugs, antidepressant, selective serotonin reuptake inhibitors (fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram and sertraline), tricyclic antidepressants, review, meta-analysis and placebo. The papers on IBS describing the clinical features, pathophysiology, evaluation, management, and clinical trials [randomised placebo-controlled trial (RCT), open-label study or case report] were selected for this review. Further literatures were also detected from references of the identified papers. The epidemiology, diagnostic criteria, pathophysiology, general management, bidirectional comorbidity, summary of currently available RCTs and open-label studies investigating antidepressant efficacy (focusing on SSRIs), and suggestions for SSRI use in IBS were relevantly synthesised based on through review of identified data. This article summarised an up-to-date clinical overview of IBS in psychiatric perspectives as well as to position a current role of SSRIs in the treatment of IBS. From this review, the routine use of SSRIs for IBS treatment cannot be conclusive due to a paucity of RCTs, although a handful of RCTs suggested a potentially beneficial effect of SSRIs over placebo.

Transdermal selegiline: the new generation of monoamine oxidase inhibitors.

The clinical use of monoamine oxidase inhibitors (MAOIs) has declined due to concerns about food and drug interactions and waning physician experience. Evidence indicates that MAOIs are effective in depressive disorders, in particular depression with atypical features. Efforts to address safety issues have led to the development of more selective and reversible MAOIs, such as moclobemide. Selegiline, a selective monoamine oxidase B inhibitor, has been approved for the adjunctive treatment of Parkinson's disease at low doses. At higher doses, oral selegiline is also effective in major depressive disorder (MDD) but loses its selectivity and has the potential for tyramine interactions. To overcome these problems, a transdermal formulation of selegiline, the selegiline transdermal system (STS), was developed with novel pharmacokinetic and pharmacodynamic properties. Compared with oral administration, transdermal selegiline leads to sustained plasma concentrations of the parent compound, increasing the amount of drug delivered to the brain and decreasing metabolite production. In addition, STS allows targeted inhibition of central nervous system monoamine A (MAO-A) and monoamine B isoenzymes with minimal effects on MAO-A in the gastrointestinal and hepatic systems, thereby reducing the risk of interactions with tyramine-rich foods (the "cheese-reaction"). Clinical trials have found 6 mg/24 hours of STS to be effective in MDD without the need for dietary restrictions. The efficacy and safety profile of STS supports its use in MDD. It is possible that STS may demonstrate benefit in MDD with atypical features or MDD resistant to other antidepressants. However, more research is needed. Clinicians should familiarize themselves with the properties and indications for the new generation of MAOIs.

Interaction analysis between 5-HTTLPR and TNFA -238/-308 polymorphisms in schizophrenia.

This study investigated the potential interaction between the polymorphisms of serotonin transporter gene (SLC6A4, a 44 base pair insertion/deletion in the promoter region, 5-HTTLPR) and tumor necrosis factor-alpha gene (TNFA; -238G/A and -308G/A polymorphisms) on the development of schizophrenia, as well as the interaction of the three polymorphisms in relation to symptomatology, family history, onset age and antipsychotic treatment response. Genomic DNA analyses with polymerase chain reaction (PCR) was used for the genotyping. One hundred and fifty-two (152) patients with schizophrenia and 152 normal controls participated in the study. Any associations between the individual polymorphism and schizophrenia were not found. However, marginal association between subjects with both TNFA -238 A allele (genotype AA plus AG) and 5-HTTLPR s allele (ss plus sl) and presence of family history was found (p = 0.023; p = 0.026). The subjects with TNFA -308 AG genotype showed higher change in PANSS total score (p = 0.028). No significant interaction effect between 5-HTTLPR and TNFA -238/-308 polymorphisms either on the development of schizophrenia or on antipsychotics treatment response and psychopathology was found, although a significant interaction effect for subjects carrying TNFA -238 AG and -308 AA genotypes on a positive family history was observed (p = 0.017). These results suggest that the interaction effects between 5-HTTLPR and TNFA -238/-308 polymorphisms gives no significant contribution to the susceptibility to schizophrenia, and is not associated with clinical variables, antipsychotic treatment response and psychopathological features, except for family history of disease, at least in the Korean population.

Tumor necrosis factor alpha gene-G308A polymorphism associated with bipolar I disorder in the Korean population.

We conducted a case-control association study between the -G308A tumor necrosis factor (TNF)-alpha gene polymorphism and 89 patients with bipolar I disorder (BID). A polymerase chain reaction method was used. We found significant differences in genotype and allele distribution. The -G308A TNF-alpha gene polymorphism may confer a risk for BID in the Korean population.

An open pilot trial of olanzapine for delirium in the Korean population.

This study was performed to assess the efficacy and safety of olanzapine for the treatment of delirium in a Korean population. An open trial of olanzapine was conducted in Korean patients with delirium caused by multiple medicosurgical conditions. All subjects were evaluated by Delirium Rating Scale (DRS), which is known to be one of the most sensitive scales for delirium. In addition, other data for profiles of side-effects were collected and analyzed. Twenty patients were treated by olanzapine with doses of 5.9 +/- 1.5 mg/day. The initial dose was 4.6 +/- 0.9 mg/day and maximal dose of olanzapine was 8.8 +/- 2.2 mg/day. The average duration of treatment was 6.6 +/- 1.7 days and the day of maximal response was 3.8 +/- 1.7 treated days. The scores of DRS were significantly improved from 20.0 +/- 3.6 at the time of pretreatment to 9.3 +/- 4.6 at the post-treatment. All subjects showed no definite serious side-effects including anticholinergic and extrapyramidal symptoms. Olanzapine treatment for patients with delirium was effective and safe. This newer drug may be a useful alternative agent to classical antipsychotics in the treatment of delirium.

Polymorphism of CTLA-4 gene for major depression in the Korean population.

This study was carried out to verify the relationship between major depression and cytotoxic T lymphocyte antigen-4 (CTLA-4), which is related to immunological function such as T-cell regulation. Among the Korean patients diagnosed with major depression according to DSM-IV, 77 patients without neurological illness, hormonal disorder, or comorbid mental illness were selected. The stored data on 149 normal Koreans from the Catholic Hemopoietic Stem Cell Bank of Korea, were used as a control group. The data of the Korean control group were compared with those of the studies of different ethnic groups. DNA was extracted from whole blood using proteinase K and the exon 1 region of CTLA-4 gene was amplified by polymerase chain reaction. Gene typing was performed using single strand conformation polymorphism. The results were assessed. There were significant differences in frequencies of CTLA-4 allele (chi2 = 56.472, d.f. = 1, P = 0.001) and genotype (chi2 = 46.132, d.f. = 2, P = 0.001) between the Korean population and the Caucasian population. However, we could not find any differences between the Korean and the Japanese population. There were no significant differences in genotype frequencies of CTLA-4*G/G, CTLA-4*G/A, and CTLA-4*A/A between the patients with major depression and the control group in the Korean population (48.1% vs. 46.3%, 41.6% vs 39.6%, 10.3% vs. 14.1%, respectively). There were no significant differences in allelic frequencies of CTLA-4*G and CTLA-4*A between the patients with major depression and the control group in the Korean population (68.8% vs. 66.1%, 31.2% vs. 33.9%, respectively). Although the present study produced negative results for the association of exon 1 polymorphism of CTLA-4 gene with major depression in the Korean population, further systematic research, including diverse clinical variables, would be necessary.