Higher Triglyceride and Normal HDL-C Concentrations, the Triglyceride/HDL-C Concentration Ratios â‰¥ 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 â‰¥ 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 patientâ€™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. Â Â
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.Â
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 â€“ 311 mg/dL beyond the normal range of TG 50 â€“ 150 mg/dL. TG-Cal/HDL-C ratios were also calculated to be in the range of 3.8 â€“ 5.9 (200/53 â€“ 311/53), probably suggesting that the patient was in the stage of insulin resistance development. The paroxetine level in the patientâ€™s serum was estimated to be in the range of 161 â€“ 387 ng/mL by calculation using formulas 75(TG-Cal â€“ 71)/46.49, 75(TG-Cal â€“ 92.25)/46.49, and 75(TG-Cal â€“ 100)/46.49, on the assumption that the patientâ€™s TG levels before paroxetine exposure were 71, 92.25, and 100 mg/dL, respectively. The paroxetine concentrations in the range of 161 â€“ 387 ng/mL were much higher than the therapeutic reference range 30 â€“ 120 ng/mL. Â Â Â
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
PAXIL (paroxetine hydrochloride) Prescribing information https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/020031s060,020936s037,020710s024lbl.pdf
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