Changsu Han

Validation of the Patient Health Questionnaire-9 Korean version in the elderly population: the Ansan Geriatric study

OBJECTIVEnWe evaluated the diagnostic validity of the 9-item depression module of the Patient Health Questionnaire-9 (PHQ-9) in elderly Korean patients and suggest an optimal cutoff score to screen for major depressive disorders.nnnMETHODnThe PHQ-9 and an elderly health questionnaire were administered to 1060 subjects older than 60 years, chosen using a stratified random sample of the community. The PHQ-9 was measured and compared with the Geriatric Depression Scale, Center for Epidemiological Studies Depression Scale, and Beck Depression Inventory scores. Reliability and validity tests, factor analysis, and receiver operating characteristic curve analysis were performed.nnnRESULTSnThe PHQ-9 indicated that 175 subjects had depressive disorders, and 885 subjects were rated as healthy. The PHQ-9 showed significant positive internal consistency (r = 0.88) and test-retest reliability (r = 0.60). The convergent validity with Geriatric Depression Scale and Center for Epidemiological Studies Depression Scale was significantly positive (r = 0.74 and 0.66, respectively). We suggest a score of 5 as the optimal cutoff point when screening for depressive disorders using the PHQ-9.nnnCONCLUSIONSnThe Korean version of the PHQ-9 is an appropriate diagnostic tool for depression, and a score of 5 is the optimal cutoff for Korean elderly subjects. Screening for depression in the elderly population using the PHQ-9 would be valuable when medically ill patients show depressive symptoms in a primary health care setting.

Does minocycline have antidepressant effect

Only one-third of patients undergoing monotherapy with an antidepressant achieve remission of their depressive symptoms and gain functional recovery. Therefore, further exploration of antidepressant mechanisms of action is important in order to facilitate the development of antidepressants with new modes of action. Preclinical and clinical studies have demonstrated that major depression is associated with impaired inflammatory responses and deficient neuroprotection. In this regard, we propose that the second-generation tetracycline minocycline may hold a potential as a new treatment for major depression. Emerging findings in animal and human studies of minocycline reveal that it has antidepressant-like neuroprotective and anti-inflammatory actions, and minocycline has been shown to perform as an antidepressant in an accepted animal model (forced swimming test). Anecdotal evidence supports minocyclines efficacy for augmentation of antidepressants in major depressive disorder. The following review describes the evidence supporting the consideration of minocycline as a potential antidepressant. We suggest that minocycline may be particularly helpful in patients with depression and comorbid cognitive impairment, as well as depression associated with organic brain disease. We also describe the antinociceptive effect of minocycline and propose a role for minocycline in the treatment of patients with major depression and prominent somatic discomfort and somatoform spectrum disorders. The lack of clinical studies of minocycline for depression is noted. Further studies of the potential therapeutic mechanism of minocycline and its therapeutic implications for major depression are warranted, and may substantially contribute to the development of newer and more effective antidepressants.

The relationship between fibromyalgia and major depressive disorder: a comprehensive review

ABSTRACT Objective: A large body of evidence suggests that the relationship between major depressive disorder (MDD) and fibromyalgia (FM) is complex. Improved understanding of this relationship promises to provide clinicians with better assessment and treatment options for both disorders. Method: This paper reviews research on the prevalence, etiology and pathogenesis, clinical characterization, and treatment of FM and MDD, as well as studies that examined the relationship between these disorders. Studies were identified via PubMed literature search. Results: Our findings point to substantial similarities in neuroendocrine abnormalities, psychological characteristics, physical symptoms and treatments between FM and MDD. However, currently available findings do not support the assumption that MDD and FM refer to the same underlying construct or can be seen as subsidiaries of one disease concept. Conclusion: New methodological and theoretical approaches may lead to a better understanding of the link between FM and MDD, and to more effective psychological and psychopharmacological therapies for FM patients. In the meantime, clinicians should carefully screen for a history of MDD in patients with FM.

The impact of the CONSORT statement on reporting of randomized clinical trials in psychiatry

To determine whether the CONSORT recommendations influenced the quality of reporting of randomized controlled trials (RCTs) in the field of psychiatry, we evaluated the quality of clinical trial reports before and after the introduction of CONSORT statement. We selected seven high impact journals and retrieved the randomized, clinical trials in the field of psychiatry during the period of 1992-1996 (pre-CONSORT) and 2002-2007 (post-CONSORT). Among the total 5201 articles screened, 736 were identified and entered in our database. After critical review of the publications, 442 articles met the inclusion and exclusion criteria. The CONSORT Index (sum of 22 items of the checklist) during the post-CONSORT period was significantly higher than that during the pre-CONSORT period. However, over 40% of post-CONSORT studies did not adhere to CONSORT statement for reporting the process of randomization, and details of the process for obtaining informed consent were still insufficient. Furthermore, adherence to the CONSORT guidelines of reporting how blinding was accomplished and evaluated actually decreased after publication of the CONSORT statement. Although the overall quality of reporting on psychiatric RCTs generally improved after publication of the CONSORT statement, reporting the details of randomization, blinding, and obtaining informed consent remain insufficient.

Fatigue as a core symptom in major depressive disorder: overview and the role of bupropion

Fatigue is one of the most common symptoms found in both community and medical care settings. Fatigue may imply a prodromal or residual symptom of major depressive disorder or an adverse reaction to antidepressant treatment. Fatigue may also compromise antidepressant treatment by delaying response to antidepressants. Despite the importance of fatigue as a core depressive symptom, data specific to the effects of fatigue on pharmacological treatment are still lacking. Bupropion is an atypical antidepressant, chemically unrelated to classical agents such as tricyclic antidepressants, selective serotonin reuptake inhibitors and other contemporary antidepressants. With a pharmacological profile that involves neurotransmitter reuptake inhibition, bupropion shares a broad range of biological properties with psychostimulants. The primary action mode of bupropion involves dopaminergic and noradrenergic neurotransmissions rather than serotonergic mechanisms, although its exact pharmacodynamic properties remain uncertain. Hence, it is possible that bupropion may play a role in the treatment of fatigue-related symptoms of major depressive disorder. This paper presents a brief overview of the clinical implications and neurobiology of major depressive disorder-related fatigue, as well as the pharmacological profile of bupropion and currently available clinical data related to its treatment of fatigue-related symptoms of major depressive disorder.

Paroxetine: safety and tolerability issues

Paroxetine is a selective serotonin re-uptake inhibitor (SSRI) available in immediate release and controlled release (CR) formulations. Paroxetine is the most potent inhibitor of serotonin re-uptake among the now available SSRIs. Paroxetine has been approved for the treatment of major depressive disorder (MDD), obsessive–compulsive disorder, panic disorder (PD), generalised anxiety disorder, post traumatic stress disorder (PTSD), and social anxiety disorder (SAD) in adults, whereas paroxetine CR is approved for the treatment of MDD, SAD, PD and premenstrual dysphoric disorder in adults. The overall efficacy of paroxetine seems to be comparable to other SSRIs in the treatment of approved indications, although paroxetine treatment induces more sedation, constipation, sexual dysfunction, discontinuation syndrome and weight gain than other SSRIs. Recent data suggest that paroxetine treatment leads to increased rates of congenital malformations, although this evidence is not conclusive. Paroxetine and paroxetine CR are not indicated for use in the paediatric population and are categorised as Pregnancy Class D. In conclusion, whether the tolerability profile of paroxetine differs substantially from other new antidepressants (including other SSRIs) needs to be determined in adequately powered well-designed randomised controlled comparative clinical trials.

Usefulness of long-acting injectable risperidone during 12-month maintenance therapy of bipolar disorder

This study aimed to assess the safety, tolerability, efficacy, and compliance of a risperidone long-acting injection (RLAI) formulation for the maintenance treatment of stabilized bipolar patients. A prospective, open-label trial of RLAI was conducted for 12 months. Stable bipolar patients (n=11) were switched from their existing oral antipsychotic agents to RLAI, and injections were given every 2 weeks. The assessments were performed at baseline and at 6 and 12 months of treatment by using the Young Mania Rating Scale (YMRS), Clinical Global Impressions-Severity of Illness (CGI-S) scale, 17-item Hamilton Rating Scale for Depression (HAM-D), Brief Psychiatric Rating Scale (BPRS), and Extrapyramidal Symptom Rating Scale (ESRS). The satisfaction levels of subjects were evaluated at the end of the study period using a 10-point visual analog scale. Ten patients (90.9%) completed the trial, and no significant changes were seen in the YMRS, HAM-D, and BPRS scores throughout the study. CGI-S and ESRS scores were significantly decreased from the baseline to the post-12-month treatment score. Relapses were not reported by any of the participants. This result indicates that RLAI may be beneficial in the maintenance therapy of stable bipolar patients; however, an adequately powered, randomized, placebo-controlled trial is necessary to draw a definite conclusion about the role of RLAI in the maintenance treatment of bipolar patients.

Venlafaxine versus mirtazapine in the treatment of undifferentiated somatoform disorder: A 12-week prospective, open-label, randomized, parallel-group trial

AbstractObjective: We set out to compare the efficacy and tolerability of mirtazapine versus venlafaxine in patients with undifferentiated somatoform disorder (USD) using the Patient Health Questionnaire-15 (PHQ-15).n Methods: This was a 12-week prospective, open-label, randomized, parallel-group trial. The trial consisted of six visits that included baseline and weeks 1, 2, 4, 8 and 12. The primary effectiveness measure was the mean change in PHQ-15 total score from baseline to the end of treatment. Secondary effectiveness measures included the mean changes in total scores on the Beck Depression Inventory (BDI) and the 12-item General Health Questionnaire (GHQ) from baseline to the end of treatment. Ninety-five subjects were randomized to either mirtazapine (n = 50) or venlafaxine (n = 45); 71 subjects completed the study (mirtazapine: n = 39/50 [78%]; venlafaxine: n = 32/45 [71%]).n Results: The mean total score on the PHQ-15 decreased by 34.7% (−8.4, p < 0.0001) from baseline to endpoint in the mirtazapine group and by 26.6% (−6.1, p < 0.0001) in the venlafaxine group. A marginally significant between-group difference was observed for the mean change in total score on the PHQ-15 from baseline to endpoint (F = 4.126, p = 0.046). The mean total scores on the GHQ-12 and BDI from baseline to endpoint decreased by −4.9 (29.4%, p < 0.0001) and −13.5 (55.9%, p < 0.0001), respectively, in the mirtazapine group, and by −4.3 (26.2%, p = 0.001) and −9.02 (46.0%, p < 0.0001), respectively, in the venlafaxine group. No between-group difference was observed for the mean changes in total scores on the secondary effectiveness measures from baseline to endpoint. Both treatments were well tolerated.n Conclusion: Our findings suggest that both mirtazapine and venlafaxine may be effective and well tolerated in the treatment of patients with USD. Double-blind, placebo-controlled and/or head-to-head comparison studies are required to allow definite conclusions to be drawn.

Does Neurotropin-3 Have a Therapeutic Implication in Major Depression?

Although several classes of antidepressants are used to treat major depression, there is an unmet need in real clinical practice because not all patients treated with an antidepressant fully recover from their functional impairment. Hence, the development of new antidepressants based on a novel therapeutic mechanism may help in the development of more effective and ideal antidepressive agents. There is emerging evidence suggesting that the etiopathogenesis of depression involves transmitters other than the major neurotransmitters such as serotonin, norepinephrine, and dopamine. Therefore, it has consistently been suggested that an alteration in neuroprotection and synaptic plasticity is associated with the pathogenesis and therapeutic mechanism of depression. Neurotropin-3 (NT3) is an interesting protein that regulates neuronal survival, synaptic plasticity, and neurotransmission. It is widely expressed in the hippocampus and facilitates hippocampal plasticity by regulating neurogenesis. It has been also reported that an infusion of NT3 increases the level of brain-derived neurotrophic factor (BDNF) mRNA expression in the cerebral cortex and produces BDNF-like effects that induce cortical tyrosine kinase B phosphorylation. BDNF has been consistently implicated in the pathogenesis of depression and the therapeutic mechanism of antidepressants. It has also been implicated in the treatment effect of mood stabilizers such as lithium. NT3 has demonstrated its possible antidepressant effect in a learned helpless animal model. Animal studies have shown that it also modulates the neurotransmitters, serotonin and noradrenaline, which are essential in the development and treatment of depression. Therefore, further studies on the therapeutic implications of NT3 for depression are warranted and are expected for the development of newer, effective antidepressants.

Is there protective haplotype of dysbindin gene (DTNBP1) 3 polymorphisms for major depressive disorder

Dysbindin gene has been repeatedly associated with psychiatric disorders and schizophrenia in particular. This study aimed to investigate the variants of dysbindin gene in major depressive disorder (MDD). One hundred and eighty eight patients with MDD and 350 controls were investigated for 4 variants within the dysbindin gene (rs3213207 A/G, rs1011313 C/T, rs760761 C/T, and rs2619522 A/C). Haplotype analyses revealed a significant association with MDD (p=0.0007, protective A-C-T-A and A-C-C-C haplotypes), in particular the effect was due to the rs760761 (C/T) and rs2619522 (A/C) haplotype (p=0.000026). These results suggest a protective effect of some dysbindin gene haplotypes on the development of MDD. Coupled with previous findings on schizophrenia, our finding suggests that dysbindin gene variants may have a role in the susceptibility to MDD. Adequately powered further studies in different ethnic groups are warranted.