OBJECTIVE: To evaluate the efficacy and safety of Jianpi Jieyu Decoction (JJD) for treating patients with mild-to-moderate depression of Xin (Heart)-Pi (Spleen) deficiency (XPD) syndrome. METHODS: In this multi-center, randomized, controlled study, 140 patients with mild-to-moderate depression of XPD syndrome were included from Xiyuan Hospital of China Academy of Chinese Medical Sciences and Botou Hospital of Traditional Chinese Medicine from December 2017 to December 2019. They were randomly divided into JJD group and paroxetine group by using a random number table, with 70 cases in each group. The patients in the JJD group were given JJD one dose per day (twice daily at morning and evening, 100 mL each time), and the patients in the paroxetine group were given paroxetine (10 mg/d in week 1; 20 mg/d in weeks 2-6), both orally administration for a total of 6 weeks. The primary outcome was the change of 17-item Hamilton Depression Rating Scale (HAMD-17) score at week 6 from baseline. The secondary outcomes included the Hamilton Anxiety Scale (HAMA) score, Traditional Chinese Medicine Symptom Scale (TCMSS), and Clinlcal Global Impression (CGI) scores at the 2nd, 4th, and 6th weekends of treatment, HAMD-17 response (defined as a reduction in score of >50%) and HAMD-17 remission (defined as a score of ⩽7) at the end of the 6th week of treatment. Adverse events (AEs) were also recorded. RESULTS: From baseline to week 6, the HAMD-17 scores decreased 10.2 ± 4.0 and 9.1 ± 4.9 points in the JJD and paroxetine groups, respectively (P=0.689). The HAMD-17 response occurred in 60% of patients in the JJD group and in 50% of those in the paroxetine group (P=0.292); HAMD-17 remission occurred in 45.7% and 30% of patients, respectively (P=0.128). The differences of CGI scores at the 6th week were not statistically significant (P>0.05). There were significant differences in HAMD-17 scores between the two groups at 2nd and 4th week (P=0.001 and P=0.014). The HAMA scores declined 8.1 ± 3.0 and 6.9 ± 4.3 points from baseline to week 6 in the JJD and paroxetine groups, respectively (P=0.905 between groups). At 4th week of treatment, there was a significant difference in HAMA between the two groups (P=0.037). TCMSS decreased 11.4 ± 5.1, and 10.1 ± 6.8 points in the JJD and paroxetine groups, respectively (P=0.080 between groups). At the 6th week, the incidence of AEs in the JJD group was significantly lower than that in the paroxetine group (7.14% vs. 22.86%, P<0.05). CONCLUSION Compared with paroxetine, JJD was associated with a significantly lower incidence of AEs in patients with mild-to-moderate depression of XPD syndrome, with no difference in efficacy at 6 weeks. (Trial registration No. ChiCTR2000040922).
Humans ; Paroxetine/adverse effects* ; Spleen ; Anxiety ; Syndrome ; Medicine, Chinese Traditional ; Treatment Outcome ; Double-Blind Method

OBJECTIVE: To observe the effect of Huayu Tongluo (resolving stasis and promoting collateral circulation) moxibustion combined with intradermal needling on depressive symptoms, quality of life and cognitive impairment in patients with mild to moderate depression after cerebral infarction on the basis of western medicine treatment. METHODS: Fifty patients with mild to moderate depression after cerebral infarction were randomly divided into an acupuncture combined with western medication group (group A, 25 cases) and a western medication group (group B, 25 cases). In the group B, paroxetine hydrochloride tablets were taken orally, 20 mg after breakfast, once a day, and the dose could be adjusted to the maximum 40 mg/d according to the patients' condition, for 4 weeks totally. On the basis of the treatment in the group B, the group A was treated with Huayu Tongluo moxibustion, namely aconite cake-separated moxibustion at Baihui (GV 20) and suspended moxibustion at Dazhui (GV 14) and Shenting (GV 24), combined with intradermal needling at Shenmen (HT 7), Jianshi (PC 5), Zusanli (ST 36), etc. Huayu Tongluo moxibustion was performed 6 times a week, and intradermal needling was performed 3 times a week，for 4 weeks totally. In the two groups, the scores of Hamilton depression scale (HAMD), stroke specific quality of life scale (SS-QOL) and mini mental state examination (MMSE) were observed before and after treatment, and the clinical efficacy and safety were compared. RESULTS: After treatment, the HAMD score in the each group was decreased compared with that before treatment (P<0.05), and that in the group A was lower than the group B (P<0.05); after treatment, the SS-QOL score in the group A and MMSE score in the two groups were increased compared with those before treatment (P<0.05), and the SS-QOL score in the group A was higher than the group B (P<0.05). The total effective rate was 88.0% (22/25) in the group A, which was higher than 60.0% (15/25) in the group B (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups (4.0% [1/25] vs 16.0%[4/25], P>0.05). CONCLUSION On the basis of the treatment of western medication paroxetine hydrochloride tablets, Huayu Tongluo moxibustion combined with intradermal needling therapy can effectively improve the depressive symptoms, quality of life and cognitive impairment of patients with mild to moderate depression after cerebral infarction.
Humans ; Moxibustion ; Quality of Life ; Paroxetine ; Depression/therapy* ; Cerebral Infarction/therapy*

Since exploding rates of modern mental diseases, application of antidepressants has increased. Worryingly, the antidepressant-induced liver injury has gradually become a serious health burden. Furthermore, since most of the knowledge about antidepressant hepatotoxicity are from pharmacovigilance and clinical case reports and lack of observational studies, the underlying mechanisms are poorly understood and there is a lack of efficient treatment strategies. In this study, antidepressant paroxetine directly triggered inflammasome activation evidenced by caspase-1 activation and downstream effector cytokines interleukin(IL)-1β secretion. The pretreatment of echinatin, a bioactive component of licorice, completely blocked the activation. This study also found that echinatin effectively inhibited the production of inflammasome-independent tumor necrosis factor α(TNF)-α induced by paroxetine. Mechanistically, the accumulation of mitochondrial reactive oxygen species(mtROS) was a key upstream event of paroxetine-induced inflammasome activation, which was dramatically inhibited by echinatin. In the lipopolysaccharide(LPS)-mediated idiosyncratic drug-induced liver injury(IDILI) model, the combination of LPS and paroxetine triggered aberrant activation of the inflammasome to induce idiosyncratic hepatotoxicity, which was reversed by echinatin pretreatment. Notably, this study also found that various bioactive components of licorice had an inhibitory effect on paroxetine-triggered inflammasome activation. Meanwhile, multiple antidepressant-induced aberrant activation of the inflammasome could be completely blocked by echinatin pretreatment. In conclusion, this study provides a novel insight for mechanism of antidepressant-induced liver injury and a new strategy for the treatment of antidepressant-induced hepatotoxicity.
Animals ; Humans ; Mice ; Antidepressive Agents/adverse effects* ; Chemical and Drug Induced Liver Injury, Chronic/prevention & control* ; Glycyrrhiza/chemistry* ; Inflammasomes/drug effects* ; Interleukin-1beta/metabolism* ; Lipopolysaccharides/toxicity* ; Mice, Inbred C57BL ; NLR Family, Pyrin Domain-Containing 3 Protein ; Paroxetine/adverse effects* ; Tumor Necrosis Factor-alpha ; Chalcones/therapeutic use*

OBJECTIVE: Treatment for panic disorder (PD) have evolved, although there is still a strong unmet need for more effective and tolerable options. The present study summarizes and discusses recent evidence regarding the pharmacological and neuromodulatory treatment of PD. METHODS: MEDLINE, Cochrane Library, PsycINFO and Thomson Reuters’s Web of Science were searched for clinical trials published between 2010 and 2018. We included all prospective experimental studies including randomized controlled trials (RCT) and other clinical trials with more than 10 patients. RESULTS: Only 11 articles met the inclusion criteria, including 4 RCT, 3 open clinical trials and 5 comparative clinical trials. RCT demonstrated efficacy of transcranial magnetic stimulation (TMS) in only one of two trials. Neither pindolol nor d-fenfluramine were effective in blocking flumazenil-induced panic attacks. Augmentation with quetiapine was not superior to placebo. Open trials indicated that escitalopram, vortioxetine and TMS may be effective. Comparative trials did not demonstrate superiority from any drug, but confirmed tranylcypromine, paroxetine, clonazepam and alprazolam as effective options. CONCLUSION: The current study confirmed the efficacy of tranylcypromine, paroxetine, clonazepam, alprazolam and escitalopram. Vortioxetine and TMS, with duration of 4 or more weeks, also seems to be effective. Quetiapine, pindolol and d-fenfluramine were not considered effective compounds.
Alprazolam ; Citalopram ; Clonazepam ; Humans ; Panic Disorder ; Panic ; Paroxetine ; Pindolol ; Prospective Studies ; Quetiapine Fumarate ; Transcranial Magnetic Stimulation ; Tranylcypromine

OBJECTIVE: South Korea made a list of potentially inappropriate medications (PIMs) for elderly patients in 2015 and has prompted medical professionals to prescribe proper medication by using the drug utilization review (DUR) system. It has been three years since the system was introduced, but related studies have rarely been conducted. This study aimed to evaluate the effect of the DUR system on the prescription of PIMs for elderly patients. METHODS: The data on the prescription of PIMs for elderly patients (≥ 65 years) who received medical treatment between March 1st and May 31st in 2015 (before introduction of the DUR system) and who received medical treatment between March 1st and May 31st in 2018 (after introduction of the DUR system) were retrospectively collected from electronic medical records. RESULTS: The prescriptions of PIMs decreased from 3,716 (7.7%) to 3,857 (6.9%) (p < 0.001). The prescription of escitalopram and paroxetine, among selective serotonin reuptake inhibitors, increased significantly, and that of short-acting benzodiazepines also increased significantly from 454 (0.93%) to 624 (1.2%). CONCLUSION: Prescription of PIMs for elderly patients significantly decreased (p < 0.001) after the DUR system was introduced. Further expanded studies of PIMs need to be conducted for the safety of elderly patients.
Aged ; Benzodiazepines ; Citalopram ; Drug Utilization Review ; Drug Utilization ; Electronic Health Records ; Humans ; Korea ; Paroxetine ; Potentially Inappropriate Medication List ; Prescriptions ; Retrospective Studies ; Serotonin Uptake Inhibitors ; Tertiary Care Centers

K⁺ channels are key components of the primary and secondary basolateral Cl- pump systems, which are important for secretion from the salivary glands. Paroxetine is a selective serotonin reuptake inhibitor (SSRI) for psychiatric disorders that can induce QT prolongation, which may lead to torsades de pointes. We studied the effects of paroxetine on a human K⁺ channel, human ether-a-go-go-related gene (hERG), expressed in Xenopus oocytes and on action potential in guinea pig ventricular myocytes. The hERG encodes the pore-forming subunits of the rapidly-activating delayed rectifier K⁺ channel (I(Kr)) in the heart. Mutations in hERG reduce I(Kr) and cause type 2 long QT syndrome (LQT2), a disorder that predisposes individuals to life-threatening arrhythmias. Paroxetine induced concentration-dependent decreases in the current amplitude at the end of the voltage steps and hERG tail currents. The inhibition was concentration-dependent and time-dependent, but voltage-independent during each voltage pulse. In guinea pig ventricular myocytes held at 36℃, treatment with 0.4 µM paroxetine for 5 min decreased the action potential duration at 90% of repolarization (APD₉₀) by 4.3%. Our results suggest that paroxetine is a blocker of the hERG channels, providing a molecular mechanism for the arrhythmogenic side effects of clinical administration of paroxetine.
Action Potentials ; Animals ; Arrhythmias, Cardiac ; Guinea Pigs ; Heart ; Humans ; Long QT Syndrome ; Muscle Cells ; Oocytes ; Paroxetine ; Salivary Glands ; Serotonin ; Tail ; Torsades de Pointes ; Xenopus

OBJECTIVE: The aim of the present study was to provide clinical consensus and evidence regarding initial treatment strategies for the pharmacological treatment of social anxiety disorder (SAD) in Korea. METHODS: We prepared a questionnaire to derive a consensus from clinicians regarding their preference for the pharmacological treatment of SAD in Korea. Data regarding medication regimens and psychotropic drugs used during initial treatment, the doses used, and the pharmacological treatment duration were obtained. Responses were obtained from 66 SAD experts, and their opinions were classified into three categories (first-line, second-line, third-line) using a chi-square analysis. RESULTS: Clinicians agreed upon first-line regimens for SAD involving monotherapy with selective serotonin reuptake inhibitors (SSRIs) or the serotonin-norepinephrine reuptake inhibitor (SNRI) venlafaxine, or combined therapy using antidepressants with betablockers or benzodiazepines on a standing or as-needed basis. First-line psychotropic drug choices for initial treatment included the following: escitalopram, paroxetine, sertraline, venlafaxine, and propranolol. The medication dosage used by domestic clinicians was found to be comparable with foreign guidelines. Domestic clinicians tended to make treatment decisions in a shorter amount of time and preferred a similar duration of maintenance treatment for SAD when compared with foreign clinicians. CONCLUSION: This study may provide significant information for developing SAD pharmacotherapy guidelines in Korea, especially in the early stage of treatment.
Antidepressive Agents ; Anxiety Disorders ; Anxiety ; Benzodiazepines ; Citalopram ; Consensus ; Drug Therapy ; Korea ; Paroxetine ; Propranolol ; Psychotropic Drugs ; Serotonin Uptake Inhibitors ; Sertraline ; Venlafaxine Hydrochloride

In patients with epilepsy, depression is a common comorbidity but difficult to be treated because many antidepressants cause pro-convulsive effects. Thus, it is important to identify the risk of seizures associated with antidepressants. To determine whether paroxetine, a very potent selective serotonin reuptake inhibitor (SSRI), interacts with ion channels that modulate neuronal excitability, we examined the effects of paroxetine on Kv3.1 potassium channels, which contribute to highfrequency firing of interneurons, using the whole-cell patch-clamp technique. Kv3.1 channels were cloned from rat neurons and expressed in Chinese hamster ovary cells. Paroxetine reversibly reduced the amplitude of Kv3.1 current, with an IC₅₀ value of 9.43 µM and a Hill coefficient of 1.43, and also accelerated the decay of Kv3.1 current. The paroxetine-induced inhibition of Kv3.1 channels was voltage-dependent even when the channels were fully open. The binding (k₊₁) and unbinding (k₋₁) rate constants for the paroxetine effect were 4.5 µM⁻¹s⁻¹ and 35.8 s⁻¹, respectively, yielding a calculated K(D) value of 7.9 µM. The analyses of Kv3.1 tail current indicated that paroxetine did not affect ion selectivity and slowed its deactivation time course, resulting in a tail crossover phenomenon. Paroxetine inhibited Kv3.1 channels in a usedependent manner. Taken together, these results suggest that paroxetine blocks the open state of Kv3.1 channels. Given the role of Kv3.1 in fast spiking of interneurons, our data imply that the blockade of Kv3.1 by paroxetine might elevate epileptic activity of neural networks by interfering with repetitive firing of inhibitory neurons.
Animals ; Antidepressive Agents ; Clone Cells ; Comorbidity ; Cricetinae ; Cricetulus ; Depression ; Epilepsy ; Female ; Fires ; Humans ; Interneurons ; Ion Channels ; Neurons ; Ovary ; Paroxetine* ; Patch-Clamp Techniques ; Rats ; Seizures ; Serotonin ; Shaw Potassium Channels* ; Tail

OBJECTIVE: The purpose of this study was to compare the efficacy and safety of escitalopram, paroxetine and venlafaxine in Korean patients with major depressive disorder (MDD). METHODS: A total of 449 Korean MDD patients were recruited in a six-week, randomized, rater-blinded, active-controlled trial and were evenly randomized to paroxetine, venlafaxine, or escitalopram treatment. RESULTS: When comparing the mean difference for the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating Scale (HDRS) total scores during six weeks, paroxetine (−6.4±0.4, and −5.4±0.4, respectively) was found to be significantly superior to escitalopram (−3.7±0.5 and −3.1±0.4, respectively). Venlafaxine had a significantly lower MADRS total score (−5.4±0.4) than escitalopram. When adjusting baseline variables, the response, according to the MADRS and HDRS scores, in the paroxetine group was greater than that for the escitalopram group (odds ratio [OR]=2.43, 95% confidence interval [CI]=1.42–4.16 for MADRS; and OR=2.32, 95% CI=1.35–3.97 for HDRS) and the venlafaxine group (OR=1.94, 95% CI=1.17–3.21 for MADRS; and OR=1.71, 95% CI=1.03–2.83 for HDRS). Despite that the overall tolerability was high and similar among the three groups, a total of 268 subjects (59.7%) prematurely discontinued treatment, representing the main limitation of the present study. CONCLUSION: Although a low study completion rate limits generalizability, our findings suggest that paroxetine might be superior to escitalopram in Korean MDD patients. Further studies should be conducted to draw a definite conclusion.
Citalopram* ; Depression ; Depressive Disorder, Major* ; Humans ; Paroxetine* ; Venlafaxine Hydrochloride*

OBJECTIVE: In this study, we investigated the determinants of remission and discontinuation of paroxetine pharmacotherapy in outpatients with panic disorder (PD). METHODS: Subjects were 79 outpatients diagnosed with PD who took 10–40 mg/day of paroxetine for 12 months. The candidate therapeutic determinants included the serotonin transporter gene-linked polymorphic region and the −1019C/G promoter polymorphism of the serotonin receptor 1A as genetic factors, educational background and marital status as environmental factors, and early improvement (EI) at 2 weeks as a clinical factor were assessed. The Clinical Global Impression scale was used to assess the therapeutic effects of the pharmacotherapy. RESULTS: Cox proportional hazards regression was performed to investigate the significant predictive factors of remission and discontinuation. EI was only a significant predictive factor of remission. EI was a significant predictive factor of remission (hazard ratio [HR], 2.709; 95% confidence interval [CI], 1.177–6.235). Otherwise, EI and marital status were significant predictive factors of the discontinuation. EI (HR, 0.266; 95% CI, 0.115–0.617) and being married (HR, 0.437; 95% CI, 0.204–0.939) were considered to reduce the risk of treatment discontinuation. In married subjects, EI was a significant predictive factor of the discontinuation (HR, 0.160; 95% CI, 0.045–0.565). However, in unmarried subjects, EI was not a significantly predictive factor for the discontinuation. CONCLUSION: EI achievement appears to be a determinant of PD remission in paroxetine treatment. In married PD patients, EI achievement also appears to reduce a risk of discontinuation of paroxetine treatment.
Drug Therapy ; Humans ; Marital Status ; Marriage* ; Outpatients* ; Panic Disorder* ; Panic* ; Paroxetine* ; Patient Dropouts ; Remission Induction ; Serotonin ; Serotonin Plasma Membrane Transport Proteins ; Single Person ; Therapeutic Uses ; Treatment Outcome*