OBJECTIVE: Pharmacogenomic-based antidepressant treatment (PGATx) may result in more precise pharmacotherapy of major depressive disorder (MDD) with better drug therapy guidance. METHODS: An 8-week, randomized, single-blind clinical trial was conducted to evaluate the effectiveness and tolerability of PGATx in 100 patients with MDD. All recruited patients were randomly allocated either to PGATx (n=52) or treatment as usual (TAU, n=48) groups. The primary endpoint was a change of total score of the Hamilton Depression Rating Scale-17 (HAMD-17) from baseline to end of treatment. Response rate (at least 50% reduction in HAMD-17 score from baseline), remission rate (HAMD-17 score ≥7 at the end of treatment) as well as the change of total score of Frequency, Intensity, and Burden of Side Effects Ratings (FIBSER) from baseline to end of treatment were also investigated. RESULTS: The mean change of HAMD-17 score was significantly different between two groups favoring PGATx by −4.1 point of difference (p=0.010) at the end of treatment. The mean change in the FIBSER score from baseline was significantly different between two treatment groups favoring PGATx by −2.5 point of difference (p=0.028). The response rate (71.7 % vs. 43.6%, p=0.014) were also significantly higher in PGATx than in TAU at the end of treatment, while the remission rate was numerically higher in PGATx than in TAU groups without statistical difference (45.5% vs. 25.6%, p=0.071). The reason for early drop-out associated with adverse events was also numerically higher in TAU (n=9, 50.0%) than in PGATx (n=4, 30.8%). CONCLUSION: The present study clearly demonstrate that PGATx may be a better treatment option in the treatment of MDD in terms of effectiveness and tolerability; however, study shortcomings may limit a generalization. Adequately-powered, well-designed, subsequent studies should be mandatory to prove its practicability and clinical utility for routine practice.
Antidepressive Agents ; Depression ; Depressive Disorder ; Depressive Disorder, Major* ; Drug Therapy ; Generalization (Psychology) ; Humans ; Precision Medicine

OBJECTIVE: This study aimed to test the possible association between cholecystokinin (CCK) promoter gene and panic disorder. METHODS: 267 patients with panic disorder and 82 healthy controls participated in this study. Genotyping was performed by polymerase chain reaction-based method. RESULTS: Genotype and allele distribution of CCK promoter -36C>T polymorphism patients with panic disorder was not significantly different from those of the controls. In addition, after excluding panic disorder patients with major depressive disorder, we did not find out the association of CCK-36C>T with the panic disorder without comorbidities. CONCLUSION: This study suggested that the CCK promoter -36C>T polymorphism may have not a potential role for susceptibility to panic disorder in the Korean population. Thus calls for consecutive studies in order to pile up the data with larger different ethnic background.
Alleles ; Cholecystokinin* ; Comorbidity ; Depressive Disorder, Major ; Diagnosis* ; Drug Therapy* ; Genotype ; Humans ; Panic Disorder* ; Panic*

OBJECTIVES: The efficacy and safety of paroxetine in the treatment of depressive disorders are well known, however its efficacy and safety for the treatment of depression in patients with cancer has been poorly studied. This study therefore aimed to evaluate the efficacy and safety of paroxetine in treatment of depressed patients with hematological malignancy (HM). METHODS: Fifty-two patients with major depressive disorder (MDD) based on DSM-IV criteria along with comorbid HM were allotted to 8 weeks trial with a flexible-dose regime of paroxetine in combination with their chemotherapy or supportive pharmacotherapy. Treatment response was assessed at baseline, week 2, week 4, and week 8 with 17-item Hamilton Rating Scale for Depression (HAM-D17), Montgomery sberg Depression Rating Scale (MADRS), and Clinical Global Impression-severity (CGI-S). Side effects were collected with the reported adverse events and laboratory test throughout the study period. RESULTS: 44.2% of 52 patients completed the eight weeks trial. Scores on the HAM-D17, MADRS, and CGI-s (last observation carried forward, LOCF) at baseline were significantly reduced with mean reduction of 30.5%, 32.8%, and 39.1%, respectively, after 8 weeks treatment with paroxetine. Forty-six patients (88.5%) reported at least one adverse event. The most common adverse event observed in this study was nausea and no serious adverse event was found. CONCLUSION: In this preliminary study, overall results showed paroxetine could be used for the treatment of depressed patients with HM, but more controlled study is needed to confirm the efficacy and safety of paroxetine in this area.
Depression* ; Depressive Disorder ; Depressive Disorder, Major ; Diagnostic and Statistical Manual of Mental Disorders ; Drug Therapy ; Hematologic Neoplasms* ; Humans ; Nausea ; Paroxetine*

Depressive Disorder, Major ; drug therapy ; psychology ; Humans ; Placebos ; therapeutic use ; Prescriptions ; Treatment Outcome

BACKGROUNDDue to safety concerns and side effects of many antidepressant medications, herbal psychopharmacology research has increased, and herbal remedies are becoming increasingly popular as alternatives to prescribed medications for the treatment of major depressive disorder (MDD). Of these, accumulating trials reveal positive effects of the spice saffron (Crocus sativus L.) for the treatment of depression. A comprehensive and statistical review of the clinical trials examining the effects of saffron for treatment of MDD is warranted.

OBJECTIVEThe purpose of this study was to conduct a meta-analysis of published randomized controlled trials examining the effects of saffron supplementation on symptoms of depression among participants with MDD.

SEARCH STRATEGYWe conducted electronic and non-electronic searches to identify all relevant randomized, double-blind controlled trials. Reference lists of all retrieved articles were searched for relevant studies.

INCLUSION CRITERIAThe criteria for study selection included the following: (1) adults (aged 18 and older) with symptoms of depression, (2) randomized controlled trial, (3) effects of saffron supplementation on depressive symptoms examined, and (4) study had either a placebo control or antidepressant comparison group.

DATA EXTRACTION AND ANALYSISUsing random effects modeling procedures, we calculated weighted mean effect sizes separately for the saffron supplementation vs placebo control groups, and for the saffron supplementation vs antidepressant groups. The methodological quality of all studies was assessed using the Jadad score. The computer software Comprehensive Meta-analysis 2 was used to analyze the data.

RESULTSBased on our pre-specified criteria, five randomized controlled trials (n = 2 placebo controlled trials, n = 3 antidepressant controlled trials) were included in our review. A large effect size was found for saffron supplementation vs placebo control in treating depressive symptoms (M ES = 1.62, P < 0.001), revealing that saffron supplementation significantly reduced depression symptoms compared to the placebo control. A null effect size was evidenced between saffron supplementation and the antidepressant groups (M ES = -0.15) indicating that both treatments were similarly effective in reducing depression symptoms. The mean Jadad score was 5 indicating high quality of trials.

CONCLUSIONFindings from clinical trials conducted to date indicate that saffron supplementation can improve symptoms of depression in adults with MDD. Larger clinical trials, conducted by research teams outside of Iran, with long-term follow-ups are needed before firm conclusions can be made regarding saffron's efficacy and safety for treating depressive symptoms.

OBJECTIVE: This study aimed to test the possible association between Cholecystokinin B receptor (CCKBR) promoter gene and panic disorder. METHODS: 262 patients with panic disorder and 76 healthy controls participated in this study. Genotyping was performed by polymerase chain reaction-based method. RESULTS: Allele distribution of CT repeat polymorphism in patients with panic disorder was not different from those of the controls. However, after excluding the patients with panic disorder comorbid with major depressive disorder and other anxiety disorder, we found out the significant association of CCKBR (CT)n repeat with the panic disorder without comorbidities. And we analysed the data as a di-allelic polymorphism with a short (140-162 bp) and a long (164-180 bp) allele. In the di-allelic analysis, there was an excess of the shorter allele in patients with panic disorder. CONCLUSION: The present study suggested that the CCKBR promoter dinucleotide polymorphism may have a potential role for susceptibility to panic disorder in the Korean population and thus calls for consecutive studies in order to pile up the data with larger different ethnic background.
Alleles ; Anxiety Disorders ; Cholecystokinin* ; Comorbidity ; Depressive Disorder, Major ; Diagnosis* ; Drug Therapy* ; Humans ; Panic Disorder* ; Panic* ; Receptor, Cholecystokinin B*

OBJECTIVES: Since the publication of Korean Medication Algorithm Project for Major Depressive Disorder (KMAP-MD) in 2002, there has been a substantial need for a revision due to rapid progress in the pharmacological management of depressive disorder. We revised KMAP-MD 2002 and developed the Korean Medication Algorithm Project for Depressive Disorder (KMAP-DD) 2006. METHODS: We developed a questionniare for surveying the opinion of experts on pharmacotherapy of depressive disorder. The questionnaire consisted of 4 parts; 1) treatment of non-psychotic depressive disorder, 2) treatment of psychotic depressive disorder, 3) treatment according to clinical subtypes and drugs choice considering adverse effects, and 4) treatment of depressive disorder in women. The questionnaire was completed by the review committee consisting of 101 experienced Korean psychiatrists. It is composed of 22 questions, and each question includes 54 sub-items. We classified the expert opinion to 3 categories (the first-line, the second-line, or the third-line) by Chi2-test. RESULTS: For depressive disorder with psychotic features, most reviewers prefer the combination of antidepressant and atypical antipsychotics. Electroconvulsive therapy and the combination of antidepressant and typical antipsychotics were the second-line treatment. Among antidepressants, venlafaxine was the most preferred, and SSRI and mirtazapine followed. Among atypical antipsychotics, quetiapine, risperidone and olanzapine were the most preferred, in this order. In patients who have no response to the first-line treatment, many reviewers recommended switching to another antidepressant or adding another atypical antipsychotics. CONCLUSION: For severe depressive disorder with psychotic features, the combination of antidepressant and atypical antipsychotics was preferred for the first-line treatment. These results suggest that the medication strategies of depressive disorder are rapidly changing and reflects the recent studies and clinical experiences.
Advisory Committees ; Antidepressive Agents ; Antipsychotic Agents ; Depressive Disorder* ; Depressive Disorder, Major ; Drug Therapy ; Electroconvulsive Therapy ; Expert Testimony ; Female ; Humans ; Psychiatry ; Publications ; Surveys and Questionnaires ; Risperidone ; Quetiapine Fumarate ; Venlafaxine Hydrochloride

BACKGROUND: Patients with schizophrenia (SCZ) and major depressive disorder (MDD) share significant clinical overlap, although it remains unknown to what extent this overlap reflects shared neural profiles. To identify the shared and specific abnormalities in SCZ and MDD, we performed a whole-brain voxel-based meta-analysis using magnetization transfer imaging, a technique that characterizes the macromolecular structural integrity of brain tissue in terms of the magnetization transfer ratio (MTR). METHODS: A systematic search based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted in PubMed, EMBASE, International Scientific Index (ISI) Web of Science, and MEDLINE for relevant studies up to March 2022. Two researchers independently screened the articles. Rigorous scrutiny and data extraction were performed for the studies that met the inclusion criteria. Voxel-wise meta-analyses were conducted using anisotropic effect size-signed differential mapping with a unified template. Meta-regression was used to explore the potential effects of demographic and clinical characteristics. RESULTS: A total of 15 studies with 17 datasets describing 365 SCZ patients, 224 MDD patients, and 550 healthy controls (HCs) were identified. The conjunction analysis showed that both disorders shared higher MTR than HC in the left cerebellum ( P =0.0006) and left fusiform gyrus ( P =0.0004). Additionally, SCZ patients showed disorder-specific lower MTR in the anterior cingulate/paracingulate gyrus, right superior temporal gyrus, and right superior frontal gyrus, and higher MTR in the left thalamus, precuneus/cuneus, posterior cingulate gyrus, and paracentral lobule; and MDD patients showed higher MTR in the left middle occipital region. Meta-regression showed no statistical significance in either group. CONCLUSIONS The results revealed a structural neural basis shared between SCZ and MDD patients, emphasizing the importance of shared neural substrates across psychopathology. Meanwhile, distinct disease-specific characteristics could have implications for future differential diagnosis and targeted treatment.
Humans ; Depressive Disorder, Major/drug therapy* ; Schizophrenia/pathology* ; Brain/pathology* ; Prefrontal Cortex ; Frontal Lobe ; Magnetic Resonance Imaging/methods*

OBJECTIVES: Major depressive disorder (MDD) patients with anhedonia tend to have a poor prognosis. The underlying imaging basis for anhedonia in MDD remains largely unknown. The relationship between nodal properties and anhedonia in MDD patients need to be further investigated. Herein, this study aims to explore differences of cerebral functional node characteristics in MDD patients with severe anhedonia (MDD-SA) and MDD patients with mild anhedonia (MDD-MA) before and after the antidepressant treatment. METHODS: Ninety participants with current MDD were recruited in this study. 24-Item Hamilton Depression Scale (HAMD-24) and Snaith-Hamilton Pleasure Scale (SHAPS) were used to assess the severity of depression and anhedonia at baseline and the end of 6-months treatment. The MDD patients who scored above the 25th percentile on the SHAPS were assigned to an MDD-SA group (n=19), while those who scored below the 25th percentile were assigned to an MDD-MA group (n=18). All patients in the 2 groups received antidepressant treatment. Functional magnetic resonance imaging (fMRI) images of all the patients were collected at baseline and the end of 6-months treatment. Graph theory was applied to analyze the patients' cerebral functional nodal characteristics, which were measured by efficiency (e_i) and degree (k_i). RESULTS: Repeated measures 2-factor ANCOVA showed significant main effects on group on the e_i and k_i values of left superior frontal gyrus (LSFG) (P=0.003 and P=0.008, respectively), and on the e_i and k_i values of left medial orbital-frontal gyrus (LMOFG) (P=0.004 and P=0.008, respectively). Compared with the MDD-MA group, the significantly higher e_i and k_i values of the LSFG (P=0.015 and P=0.021, respectively), and the significantly higher e_i and k_i values of the LMOFG (P=0.015 and P=0.037, respectively) were observed in the MDD-SA group at baseline. Meanwhile, higher SHAPS scores could result in higher e_i and k_i values of LSFG (P=0.019 and P=0.026, respectively), and higher e_i value of LMOFG (P=0.040) at baseline; higher SHAPS scores could result in higher e_i values of LSFG (P=0.049) at the end of 6-months treatment. The multiple linear regression analysis revealed that sex were negatively correlated with the e_i and k_i values of LSFG (r= -0.014, P=0.004; r=-1.153, P=0.001, respectively). The onset age of MDD was negatively correlated with the k_i value of LSFG (r=-0.420, P=0.034) at the end of 6-months treatment. We also found that SHAPS scores at baseline were positively correlated with the HAMD-24 scores (r=0.387, P=0.022) at the end of 6-months treatment. CONCLUSIONS There are obvious differences in nodal properties between the MDD-SA and the MDD-MA patients, such as the high e_i of LSFG in the MDD-SA patients, which may be associated with the severity of anhedonia. These nodal properties could be potential biomarkers for the prognosis of MDD. The increased e_i and k_i values in the LSFG of MDD-SA patients may underlie a compensatory mechanism or protective mechanism. The mechanism may be an important component of the pathological mechanism of MDD-SA. The poor prognosis in the MDD-SA patients suggests that anhedonia may predict a worse prognosis in MDD patients. Sex and onset age of MDD may affect the nodal properties of LSFG at baseline and the end of 6-months treatment.
Anhedonia ; Antidepressive Agents/therapeutic use* ; Depressive Disorder, Major/drug therapy* ; Humans ; Infant ; Infant, Newborn ; Magnetic Resonance Imaging ; Prefrontal Cortex

OBJECTIVE: In 2002, the Korean Society for Affective Disorders developed the guidelines for the treatment of major depressive disorder (MDD), and revised it in 2006 and 2012. The third revision of these guidelines was undertaken to reflect advances in the field. METHODS: Using a 44-item questionnaire, an expert consensus was obtained on pharmacological treatment strategies for MDD 1) without or 2) with psychotic features, 3) depression subtypes, 4) maintenance, 5) special populations, 6) the choice of an antidepressant (AD) regarding safety and adverse effects, and 7) non-pharmacological biological therapies. Recommended first, second, and third-line strategies were derived statistically. RESULTS: AD monotherapy is recommended as the first-line strategy for non-psychotic depression in adults, children/adolescents, elderly adults, patient with persistent depressive disorder, and pregnant women or patients with postpartum depression or premenstrual dysphoric disorder. The combination of AD and atypical antipsychotics (AAP) was recommended for psychotic depression in adult, child/adolescent, postpartum depression, and mixed features or anxious distress. Most experts recommended stopping the ongoing initial AD and AAP after a certain period in patients with one or two depressive episodes. As an MDD treatment modality, 92% of experts are considering electroconvulsive therapy and 46.8% are applying it clinically, while 86% of experts are considering repetitive transcranial magnetic stimulation but only 31.6% are applying it clinically. CONCLUSION: The pharmacological treatment strategy in 2017 is similar to that of Korean Medication Algorithm for Depressive Disorder 2012. The preference of AAPs was more increased.
Adult ; Aged ; Antipsychotic Agents ; Biological Therapy ; Consensus ; Depression ; Depression, Postpartum ; Depressive Disorder ; Depressive Disorder, Major ; Drug Therapy ; Electroconvulsive Therapy ; Female ; Humans ; Mood Disorders ; Pregnant Women ; Premenstrual Dysphoric Disorder ; Transcranial Magnetic Stimulation