Paroxetine is a selective 5-hydroxytryptamine reuptake blocker (SSRIS), a new antidepressant with good efficacy and few adverse effects. Some large clinical studies have confirmed that it can also be used to treat panic attacks, generalized anxiety disorder, social anxiety disorder, obsessive-compulsive disorder (OCD), insomnia, premenstrual syndrome (PMS), and premature ejaculation and other disorders. Paroxetine (paroxetine) is a selective 5-hydroxytryptamine (5-HT) reuptake blocker (SSRIS) that was reported in 1991 in the American Journal of Drugs to be used in the treatment of depression. In recent years, a large number of clinical studies have found that it can also be used to treat panic attacks, generalized anxiety disorder, social anxiety disorder, obsessive-compulsive disorder, insomnia, premenstrual syndrome, premature ejaculation, and other disorders. It is summarized below. Pharmacological effects Paroxetine exerts its effects by inhibiting 5-HT reuptake in brain neurons, and is more selective than tricyclic antidepressants (TCAs), fluoxetine, and sertraline, and rarely acts through other neurotransmitters. Low affinity for histamine H1 receptors, adrenergic α or β receptors, dopamine D2 receptors, paroxetine does not act on norepinephrine (NA) receptors in the brain, suggesting that the drug’s sedative effect is small, and the impairment of cognitive processes or psychomotor function is also small, the affinity for cholinergic receptors and cardiovascular adverse effects are less than TCAs, and there are no specific alterations of the hematologic, biochemical, and urologic systems with short- or long-term treatment. No specific alterations. Pharmacokinetics Paroxetine is completely absorbed orally in the gastrointestinal tract and is not affected by food or the combined use of antacids. Because of the phenylpiperidine compounds, with lipophilic properties can be rapidly and widely distributed in all tissues of the body, including the central nervous system, only 1% of the presence of the body circulation. Peak plasma concentration can be reached within 2~10h after oral administration, T1/2 is 20 h, 20mg oral daily, in 7~14d can reach steady state plasma concentration, the therapeutic concentration of paroxetine plasma protein binding rate of about 95%, a fixed dose of paroxetine in the elderly plasma concentration is higher than that in the young 78%. Paroxetine enters the infant through breast milk, and when administered orally to a nursing woman at 20-40 mg d-1, the amount in the infant is less than 1.0%-2.0% of the maternal intake. It is mainly metabolized by hepatic first-pass metabolism, oxidized to unstable catecholamine intermediates, then methylated, and finally combined with glucuronic acid to form uridylate, which is an inactive metabolite, most of which is excreted through the urinary tract (64%), while a small amount is excreted by bile with feces. Clinical efficacy of paroxetine Depression Paroxetine can be used to treat all types of depression; it is commonly dosed at 20 mg per day, with weekly increments of 10 mg in refractory cases, and a maximum dose of 50 mg per day, depending on the clinical response and tolerability. Paroxetine is similar in efficacy to the TCAs, with fewer adverse effects than the TCAs. feighner et al. conducted a double-blind controlled study in 717 depressed patients. Double-blind controlled study found that wk6 end Hamilton depression scale (HAMD) score reduction rate: paroxetine group for 37.9%, promethazine group for 35.1%, placebo group for 21.8%; and at the end of wk2 paroxetine group Hamilton anxiety scale (HAMA) and HAMD are compared with the placebo group and the promethazine group have significant improvement, can be seen in the efficacy of paroxetine and promethazine are similarly superior to the placebo group, but paroxetine and promethazine have similar efficacy. It is evident that paroxetine and promethazine have similar efficacy and are better than the placebo group, but paroxetine acts earlier than promethazine and has a significant anxiolytic effect. In the randomized double-blind controlled study of the antidepressant effects of paroxetine and amitriptyline, chlorpromazine, doxorubicin, and maprotiline, no difference in efficacy was found between them, but the incidence of adverse reactions in the paroxetine group was low. The efficacy of paroxetine and fluoxetine was similar, but paroxetine had better efficacy on anxiety and insomnia accompanying depressed patients.TIG- NOL randomized double-blind controlled study of 78 depressed patients showed that 68% of patients in the paroxetine group and 63% of patients in the fluoxetine group had ≥50% of HAMD subtraction rate, but at the end of wk3, 36% of the patients in the paroxetine group and 16% of the patients in the fluoxetine group had HAMD subtraction rate ≥ 50% (P< 0.05). (P< 0.05), as well as a significant improvement in anxiety factors in the paroxetine group. Short-term treatment of panic attacks Many studies have shown that paroxetine short-term treatment of panic attacks and chlorpromazine efficacy is comparable and earlier action, better than placebo.LECRUBIER et al. 367 cases of panic attacks patients in 12 wk of randomized double-blind controlled study, 50.9% of the paroxetine group, chlorpromazine group 36.7%, the placebo group of 31.6% of the patients were cured, the results show that the efficacy of paroxetine and chlorpromazine group of 31.6% of the patients, the results show that paroxetine and placebo group, the results are the same as those of the other patients, the results of the other patients. BAKKER et al. showed that paroxetine (20～60mg・d-1) and chlorpromazine (50～150 mg・1・d) had similar efficacy and were significantly better than placebo in 131 cases, and paroxetine was also significantly better than cognitive-behavioral therapy, and there was no significant difference between cognitive-behavioral therapy and placebo. 66% of the patients in the paroxetine group no longer had panic attacks and functioned better than the placebo group. In the paroxetine group, 66% of patients no longer had panic attacks and they worked earlier. In a study of different doses of 10, 20, and 40 mg/d-1, 40 mg was more effective than placebo, although patients responded to the lower dose, and in the last 2 wk, 86% of patients in the paroxetine 40 mg/d-1 group and 50% of those in the placebo group (P<0.01) stopped having seizures completely, a highly significant difference. Long-term treatment Some studies have shown that long-term treatment of panic attacks with paroxetine can significantly reduce the number of attacks and prevent recurrence for 6-9 mo. LECRUBIER et al. observed 36 wk of continuous treatment for 176 patients who had completed 12 wk of treatment for panic attacks, and at the end of wk 24, the reduction in the score of the paroxetine group, the clopromazine group, and the placebo group was 15.3, 12.1, and 10.2, respectively. The number of cured cases was 77.8%, 77.6%, and 65.1%, respectively, with no significant difference among the three groups; at the end of wk 36, the cure rates of the three groups were 84.6%, 83.9%, and 59.1%, respectively, which showed that the efficacy of paroxetine was similar to that of chlorpromazine and superior to that of placebo. In all treatment groups, the number of cured cases increased gradually. Generalized anxiety disorder (GAD) paroxetine can effectively treat GAD, ROCCA et al. 81 cases of GAD patients randomized double-blind controlled study, were given paroxetine 20mg・d-1, promethazine 50 ~ 100mg・d-1, clonazepam 3 ~ 6mg・d-1 treatment for 12wk, the results show: 68% of the paroxetine group, 72% of the promethazine group, 55% of the clonazepam group. The results showed that 68% of patients in the paroxetine group, 72% in the promethazine group, and 55% in the clonazepam group had a HAMA score reduction rate of ≥50%, whereas the adverse effects of promethazine were significantly higher than those of the paroxetine group, and the paroxetine group was superior to clonazepam in terms of reducing psychiatric anxiety and similar to that of promethazine after 4 wk. A domestic comparative study of 90 cases showed that paroxetine efficacy was superior to clonazepam or alprazolam, effective for both somatic and psychiatric anxiety, and more pronounced improvement in psychiatric anxiety symptoms. Social anxiety disorder (i.e., social phobia) Paroxetine was the first SSRI to be studied in a large-scale, placebo-controlled clinical trial for the treatment of social anxiety disorder.BALDWIN et al.'s randomized, double-blind study of 290 patients with social anxiety disorder demonstrated a reduction in the LIEBOWITZ Social Anxiety Scale (LSAS) total score from -29.4 to -5.6 in the paroxetine group (P< 0.001), with efficacy rates of 65.7% and 32.4% in the paroxetine and placebo groups, respectively (P<0.001). Paroxetine was significantly better than placebo in controlling anxiety and avoiding morbid fear, and patients in the paroxetine group showed a significant improvement in their ability to work and live socially. Obsessive-compulsive disorder (OCD) Clinical studies have shown that the efficacy of paroxetine in the treatment of OCD is comparable to that of chlorpromazine and is more effective than that of placebo.ZOHAR et al. randomized, double-blind study of 399 patients with OCD showed that in the paroxetine group, the chlorpromazine group, and the placebo group, respectively, 55.1%, 55.3%, and 35.4% of the patients had a reduction of ≥50% in their Yale-Brown Obsessive-Compulsive Scale (YBOCS) score, indicating that paroxetine 10-10% of patients had a reduction of ≥50% in YBOCS score. The YBOCS scores of 55.1%, 55.55% and 35.4% of patients in the OCD group had Yale-Brown Obsessive-Compulsive Scale (YBOCS) score reductions of ≥50% respectively, which showed that the efficacy of paroxetine 10-60 mg ・d-1 and chlorpromazine 25-250 mg ・d-1 was similar, and they were both significantly better than that of placebo, but the chlorpromazine group had more adverse effects, especially anticholinergic adverse effects.Goder et al. treated 348 OCD patients for 12 wk with either placebo or paroxetine 20, 40, and 60 mg ・d-1 respectively. The mean YBOCS reduction scores were 3.4, 4.2, 6.4 and 7.3, respectively. paroxetine 40-60mg was significantly more effective than placebo (P<0.05), and 60mg・d-1 was significantly more effective than 20mg・d-1 (P<0.05). Some data show that paroxetine can sustain treatment and prevent relapse for more than 1a. Primary insomnia Paroxetine can effectively treat insomnia. NOWELL et al. 14 cases of primary insomnia patients, the application of paroxetine 5-30mg・d-1 treatment 6wk, by the Pittsburgh Sleep Quality Index (PSQI) score and sleep polysomnography assessment of the efficacy of the results show that: 14 cases of patients, 11 cases of improvement, of which 7 cases were cured, shortening of the time of falling asleep, prolongation of the sleep time, the self-assessment of the quality of sleep and daytime function are significantly improved The results show that paroxetine can effectively treat insomnia. The treatment of paroxetine in depressed patients resulted in improved sleep quality and daytime functioning, which was easily accepted by patients. The shortcomings of this study are the absence of a control group and the small number of cases; a large-sample, randomized, double-blind, placebo-controlled clinical study is necessary. Premenstrual syndrome in women (PMDD) Paroxetine has been documented to be used in the treatment of PMDD. erikson et al. randomized 65 patients with PMDD to a double-blind treatment for 3 menstrual cycles, and showed that paroxetine was significantly superior to maprotiline and placebo. 18 patients with PMDD who received paroxetine 5-30 mg・d-1 for 10 menstrual cycles showed significant improvements in premenstrual irritability The premenstrual symptoms of irritability, depressive mood, increased appetite, and anxiety were significantly lower than before treatment, and there were no significant changes in adverse effects on sexual function after 10 menstrual cycles. Chronic headache FOSTER et al. 48 cases of chronic headache patients with paroxetine 10-50mg・d-1 treatment 3-9mo, 92% of the patients monthly headache episodes reduced by ≥ 50%. LANGEMARK et al. double-blind controlled study of paroxetine 20 ~ 30mg・d-1 and sulpiride 200 ~ 400mg・d-1 treatment of 50 patients with chronic tension headache without depression, 8wk end of the headache was significantly reduced, but sulpiride than paroxetine to reduce the obvious. Premature Ejaculation Paroxetine delays ejaculation time and can be used clinically to treat premature ejaculation.WALDINGER et al. reported 2 randomized double-blind controlled studies. In the first part of the study, 60 patients who consistently had premature ejaculation during sexual intercourse were randomized and given fluoxetine 20 mg・d-1, fluvoxamine 100 mg・d-1, paroxetine 20 mg・d-1, sertraline 50 mg・d-1, or a placebo for 6 wk, and were allowed to keep track of the time of ejaculation by themselves. The results showed that paroxetine had the strongest delayed ejaculation effect compared to the pre-drug period. In the second part of the study, those with a previous history of premature ejaculation were compared with those with a history of premature ejaculation and were randomized to paroxetine 20 mg d-1 or placebo. The results showed that the delayed ejaculatory effect of paroxetine was not only found in those with a history of premature ejaculation, but also in those who had a normal ejaculation time in the past. McMAHON et al. 2 clinical studies also confirmed that paroxetine can significantly prolong the time of ejaculation in patients with premature ejaculation, with a highly significant difference compared with placebo. ABDEL-HAMID et al. 31 patients with premature ejaculation found that paroxetine prolonged the time of ejaculation in patients with premature ejaculation, with an efficacy similar to that of promethazine, which was superior to that of manual therapy. Others Some other reports have shown that paroxetine may be effective in the treatment of intractable vasovagal syncope, post-traumatic stress disorder, alcohol dependence, etc. Adverse Reactions General Adverse Reactions Adverse reactions to paroxetine are rare and mild, and may include mild dry mouth, anorexia, nausea, constipation, dizziness, tremor, malaise, and sexual dysfunction. Nausea is the most common adverse reaction, the incidence of 40%; dry mouth and constipation and other anticholinergic effects occur less frequently than TCAs, the incidence of 8% and 8%, respectively. A study of 934 cases of long-term treatment with paroxetine found that the more common adverse reactions were: headache (19%), sweating (14%), dizziness (2%), insomnia (12%), drowsiness (12%). Delayed ejaculation and impotence have been reported in 10% of men and sexual dysfunction in 2% of women, more than in other SS RIs, all of which gradually diminished or disappeared after 3 wk and did not affect treatment. There was no significant difference in the adverse effects of paroxetine 20-30 mg・ d-1, fluoxetine 20 mg・ d-1 and sertraline 50-20 mg・ d-1. Serious adverse reactions Serious adverse reactions to paroxetine have been reported less frequently, with occasional angioneurotic edema, hepatitis, upright hypotension, tremor, and extrapyramidal symptoms, and there are other reports of hyponatremia occurring in 1/200 of older adults over 65a treated with paroxetine each year, with low body weight being a risk factor for hyponatremia, with many cases occurring within 3 wk of treatment. Withdrawal Symptoms Withdrawal of paroxetine after 6mo or more of treatment, i.e., at the end of a period of continuous therapy, is more likely to result in a regular withdrawal reaction than during 4-8 wk of acute treatment. Clinical manifestations dizziness, vertigo, unsteady walking, nausea, vomiting, diarrhea, fatigue, myalgia, nasal discharge, and malaise persist for up to 3 wk (12 d on average), and are relieved by restarting treatment for 24 h, and by taking benzodiazepines, and there is no increase in the risk of withdrawal syndrome for shorter than 7 wk of treatment without regularizing the symptoms of withdrawal, but longer than 6 mo. Adverse effects in the elderly The application of paroxetine in the elderly caused no significant increase in adverse effects compared with those of lower age, but there is a risk of hyponatremia, the application of paroxetine versus TCAs treatment, the frequency of adverse effects was 61% and 74%, respectively (P < 0.05). Paroxetine had significantly fewer adverse reactions compared to TCAs. Drug interactions Paroxetine is unaffected by food and antacids. As with other 5-HT reuptake blockers, the use of paroxetine with monoamine oxidase inhibitors (MAOIs) can cause 5-HT syndrome (serotonin syndrome), which manifests itself in the following ways: hyperthermia, nausea, profuse sweating, autonomic dysfunction, confusion, tremor, myoclonus, coma, and even death. To avoid this serious adverse effect, at least 2 wk interval is required when co-administered with MAOI. Paroxetine has a strong inhibitory effect on CYP2D6, which can increase the blood concentration of concomitantly administered drugs that are metabolized by this enzyme: e.g., adrenergic β-receptor blocking drugs, 1CAs, antipsychotics (haloperidol, fenestrazine, risperidone, thioridazine), antiarrhythmics (mesiuria, propafenone, scammon), fludrocamidol, antipsychotic (fludrocalcitone), and antidysrhythmic (mesiuria, propafenone, skelaromide), and antipyretic, flutamide), opiates, SSRIs (fluoxetine, desmethylcitalopram), and others. Weak inhibition of CYP1A2 and CYP3A3/4. Dosage and Administration The starting dose of paroxetine is 10-20mg・ d-1, taken at breakfast, and if the efficacy is poor within 2-3wk, it can be increased at a rate of 10mg per week to 50mg・ d-1, which is also the maximum dose. Paroxetine may be taken with food to minimize gastrointestinal reactions. The effective and adherent dose of paroxetine is 30mg・d-1, and the dose for the elderly and those with hepatic or renal impairment is 20mg・d-1. Discontinuation of paroxetine is similar to that of other psychotropic medications, with a gradual reduction in dosage and no abrupt stopping. To summarize, paroxetine is a new type of antidepressant with dual action, with good efficacy, few adverse effects, high compliance, and good efficacy in panic attacks, generalized anxiety disorder, social anxiety disorder, obsessive-compulsive disorder, insomnia, premenstrual syndrome, premature ejaculation and other diseases.