When to Choose Paroxetine Treatment in Skin-Picking Disorder: A Case Report

Skin picking disorder (SPD) characterized by repetitive compulsive scratching in the absence of a primary skin disease is strongly associated with psychiatric comorbidities, including obsessive-compulsive disorder (OCD) and depression (MDD). Selective serotonin reuptake inhibitors (SSRIs) have been used in the treatment of SPD with variable success. Nevertheless, the optimum treatment choice for SPD is an issue for clinicians. This case report presents a 32-year-old female SPD patient treated with four-week paroxetine monotherapy. Based upon the clinical interview and standardized questionnaires, the patient was diagnosed with OCD with depressive features and Skin Picking Disorder. In addition to symptom severity scales, quantitative electroencephalography (qEEG) was also applied. Paroxetine treatment was started (titrated from 5 to 40 mg/day) and doubled each week. After four-week paroxetine monotherapy, OCD symptoms were diminished, and skin lesions were completely regressed leaving solely post inflammatory hyperpigmentation. Post-treatment qEEG assessment also showed a normalization of frontal alpha power and amplitude asymmetry. It can be concluded that if OCD includes SPD with abnormal EEG patterns; then the treatment success using paroxetine will be very high.

Effects of paroxetine on biochemical parameters and reproductive function in male rats

Selective serotonin reuptake inhibitors (SSRI) are a class of molecules used in treating depression, anxiety, and mood disorders. Paroxetine (PRT) is one of the most prescribed antidepressants, which has attracted great attention regarding its side effects in recent years. This study was planned to assess the adverse effects of paroxetine on the biochemical parameters and reproductive system. Fourteen male Wistar rats were randomly allocated into two groups (7 rats for each): control and treated with paroxetine at a dose of 5mg/kg.bw for two weeks. At the end of the experiment, blood was collected from the retro-orbital plexus for measuring the biochemical parameters, whereas the reproductive organs were removed for measuring semen quality and the histological investigations. Results showed that paroxetine induced significant changes in some biochemical parameters and alteration of semen quality, including sperm count, spermatids number and sperm viability, motility and abnormalities. The histopathological examinations of testis and epididymis revealed an alteration of spermatogenesis, cellular disorganization and vacuolization, enlargement of interstitial space, shrinkage and degenerative changes in the epithelium of seminiferous and epididymal tubules with few to nil numbers of spermatozoa in their lumen. In conclusion, paroxetine treatment caused changes in some biochemical parameters and sperm profiles as well as histopathologic effects of reproductive organs.

White Matter Microstructure Alterations Associated With Paroxetine Treatment Response in Major Depression

More than one-third of depressive patients do not achieve remission after the first antidepressant treatment. The “watch and wait” approach used to find the most effective antidepressant leads to an increased personal, social, and economic burden in society. In order to overcome this challenge, there has been a focus on studying neural biomarkers associated with antidepressant response. Diffusion tensor imaging measures have shown a promising role as predictors of antidepressant response by pointing to pretreatment differences in the white matter microstructural integrity between future responders and non-responders to different pharmacotherapies. Therefore, the aim of the present study was to explore whether response to paroxetine treatment was associated with differences in the white matter microstructure at baseline. Twenty drug-naive patients diagnosed with major depressive disorder followed a 6- to 12-week treatment with paroxetine. All patients completed magnetic resonance brain imaging and a clinical assessment at baseline and 6–12 weeks after treatment. Whole-brain tract-based spatial statistics was used to explore differences in white matter microstructural properties estimated from diffusion magnetic resonance imaging. Voxel-wise statistical analysis revealed a significant increase in fractional anisotropy and a decrease in radial diffusivity in forceps minor and superior longitudinal fasciculus in responders compared to non-responders. Thus, alterations in white matter integrity, specifically in forceps minor and the superior longitudinal fasciculus, are associated with paroxetine treatment response. These findings pave the way for personalized treatment strategies in major depression.

Paroxetine Attenuates Cardiac Hypertrophy Via Blocking GRK2 and ADRB1 Interaction in Hypertension

Background ADRB1 (adrenergic receptor beta 1) responds to neuroendocrine stimulations, which have great implications in hypertension. GRK2 (G protein‐coupled receptor kinase 2) is an essential regulator for many G protein‐coupled receptors and subsequent cell signaling cascades, but its role as a regulator of ADRB1 and associated cardiac hypertrophy in hypertension remains to be elucidated. Methods and Results In this study, we found the expressions of GRK2 and ADRB1 in peripheral blood mononuclear cells were positively associated with blood pressure levels in hypertensive patients and with their expression in heart. In vitro evidence showed a direct interaction in ADRB1 and GRK2 and genetic depletion of GRK2 blocks epinephrine‐induced upregulation of hypertrophic and fibrotic genes in cardiomyocytes. Meanwhile, we discovered a selective serotonin reuptake inhibitor paroxetine specifically blockades GRK2 and ADRB1 interaction. In vivo, paroxetine treatment ameliorates hypertension‐induced cardiac hypertrophy, dysfunction, and fibrosis in animal models. We found that paroxetine suppressed sympathetic overdrive and increased the adrenergic receptor sensitivity to catecholamines. Paroxetine treatment also blocks epinephrine‐induced upregulation of hypertrophic and fibrotic genes as well as ADRB1 internalization in cardiomyocytes. Coadministration of paroxetine further potentiates metoprolol‐induced reductions in blood pressure and heart rate, further attenuating cardiac hypertrophy in spontaneously hypertensive rats. Furthermore, in patients with hypertension accompanied with depression, we observed that cardiac remodeling was less severe in those with paroxetine treatment compared with those with other types of anti‐depressive agents. Conclusions Paroxetine promotes ADRB1 sensitivity and attenuates cardiac hypertrophy partially via blocking GRK2‐mediated ADRB1 activation and internalization in the context of hypertension.

Higher Triglyceride and Normal HDL-C Concentrations, the Triglyceride/HDL-C Concentration Ratios ≥ 3.5, and Insulin Resistance as Potential Predictors of Developing Higher Paroxetine Concentrations and Suicide in the Early Months of Medication

Background: There are several reported results. Hazard ratios for suicide tended to increase with dose for selective serotonin reuptake inhibitors (SSRIs). The suicide rate in the first three months following initiation of paroxetine exposure was 799 per 100,000 person-years, while, annual suicide rates for depression and anxiety were 81.8 and 76.7, respectively. SSRIs serum concentrations were significantly associated with increases of triglyceride (TG) levels. SSRIs inhibited insulin signaling and beta cell function by a dose-dependent manner.Objective: Based on symptoms and blood lipid levels indicated by a young patient who committed suicide, my objective is to propose that higher TG concentrations above the normal range, normal high-density lipoprotein cholesterol (HDL-C) concentrations, and the TG/HDL-C concentration (mg/dL) ratios ≥ 3.5 to estimate insulin resistance are potentially useful in identifying individuals who are developing higher paroxetine concentrations.Methods: The glucose and lipid levels in the blood examination which was performed in an emergency hospital to where the patient was delivered by ambulance after his abnormal behaviors on the 14th day after the start of paroxetine treatment, were used for calculation and examination. Fasting TG levels were estimated by calculating TG values (TG-Cal) using the measured value of TG and a formula reported by Hitze et al., or the measured values of total cholesterol (TC), HDL-C, and low-density lipoprotein cholesterol (LDL-C), and nine formulas referred and reported by Dansethakul et al. Paroxetine levels in the patient’s serum were estimated by calculation using the regression coefficient of TG 46.49 mg/dL, with which the paroxetine serum concentration 75 ng/mL was associated in the results reported by Fjukstad et al.   Results: The 20-year-old patient free of recent suicidal ideation developed intense violent suicidal preoccupation, and exhibited abnormal behaviors in the first 41 days after the start of paroxetine treatment 10 mg twice daily. He sent emails with advanced notice of suicide to his friend on the 7th, 17th, and 18th days, drank alcohol alone and exhibited abnormal behaviors in a market place around noon, blacked out, and was ambulanced to the emergency hospital on the 14th day. Finally, he carried out suicide on the 41st day after three days of abrupt discontinuation of paroxetine. He never exhibited these abnormal behaviors before paroxetine exposure. The levels of glucose, TG, TC, HDL-C, and LDL-C measured in the blood examination at 15:56 on the 14th day after the start of paroxetine treatment were 111, 498, 185, 53, and 92 mg/dL, respectively. The levels of TC, HDL-C, and LDL-C were in the normal ranges, respectively, probably suggesting metabolic normality of the patient before paroxetine exposure. In order to estimate the fasting TG level, TG-Cal values were calculated to be 278, 200, 258, 240, 268, 272, 310, 308, 311, and 250 mg/dL in the range of 200 – 311 mg/dL beyond the normal range of TG 50 – 150 mg/dL. TG-Cal/HDL-C ratios were also calculated to be in the range of 3.8 – 5.9 (200/53 – 311/53), probably suggesting that the patient was in the stage of insulin resistance development. The paroxetine level in the patient’s serum was estimated to be in the range of 161 – 387 ng/mL by calculation using formulas 75(TG-Cal – 71)/46.49, 75(TG-Cal – 92.25)/46.49, and 75(TG-Cal – 100)/46.49, on the assumption that the patient’s TG levels before paroxetine exposure were 71, 92.25, and 100 mg/dL, respectively. The paroxetine concentrations in the range of 161 – 387 ng/mL were much higher than the therapeutic reference range 30 – 120 ng/mL.    Conclusions: The above results probably suggest that paroxetine exposure, higher TG concentration, higher paroxetine concentration, and suicide coincided in the patient. Follow-up measurements of TG and HDL-C concentrations and the TG/HDL-C ratios have a potential to predict and prevent suicides in the early months of paroxetine exposure.Â