Paroxetine and amitriptyline in the treatment of depression in general practice

Christiansen PE, Behnke K, Black CH, Öhrström JK, Bork-Rasmussen H, Nilsson J. Paroxetine and amitriptyline in the treatment of depression in general practice. Acta Psychiatr Scand 1996: 93: 158–163. © Munksgaard 1996. A total of 144 outpatients in general practice in Denmark, aged 18–65 years and diagnosed as suffering from depression with a HAMD-17 score of 15 or more, were included in this 8-week double-blind, randomised, multicentre, controlled, parallel group comparison of paroxetine versus amitriptyline. The purpose of the study was primarily to evaluate efficacy and tolerance of treatment. In addition, focus was added on weight change and subjective well-being. The efficacy results showed equal effect of both drugs. However, paroxetine was tolerated better than amitriptyline, and this difference reached the level of significance when four non-evaluable patients were taken out of the analysis. Moreover, there was a significant weight increase in the amitriptyline group and no significant weight change in the paroxetine group. There was no difference between the groups as regards subjective well-being as measured by the VAS. In conclusion, paroxetine is an effective and well-tolerated antidepressant, and well-suited for the treatment of depression in general practice.     

Measures of serotonin metabolism in anorexia nervosa.

Thirty-five consecutive attenders at a clinic specializing in anorexia nervosa were studied. All conformed to a DSM-III-R diagnosis for anorexia nervosa. In addition, 3 cases suffered from major depressive disorder and 9 from dysthymia. Blood from all patients was analysed for monoamine oxidase, serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), tryptophan and platelet paroxetine binding. Findings showed that blood 5-HT was higher than normal in all patient groups, and was highest in those having affective disorder with anorexia nervosa. However, of the patients with anorexia nervosa alone, a subgroup having greatest weight loss had blood 5-HT levels significantly below all other groups. Lack of significant changes in other parameters compared with normal subjects points to the possibility of abnormal 5-HT storage or release.     

Sulpiride and Paroxetine in the Treatment of Chronic Tension-Type Headache. An Explanatory Double-Blind Trial

SYNOPSIS
Drugs influencing monoaminergic pathways are of potential use in the treatment of pain.
A serotonin re-uptake inhibitor, paroxetine (20-30 mg daily), and a dopamine antagonist, sulpiride (200-400 mg daily) were compared in a randomized, double-blind, response-conditional cross-over pilot study in 50 non-depressed patients with chronic tension-type headache.
Headache was scored daily on a 5-point verbal scale during 4-weeks baseline and during 8 weeks of treatment for each drug. A 5-point 'Global' assessment was obtained for each drug, In both treatment groups headache score decreased compared to baseline.
Group comparison of 24 patients first treated with paroxetine and 24 patients first treated with sulpiride showed a non-significant trend in favor of sulpiride by 'Global' evaluation and by evaluation of the available diary records (18 paroxetine-treated and 19 sulpiride-treated).
Cross-over analysis of 'Global' records from 20 patients treated with paroxetine followed by sulpiride and 17 patients treated in the reverse order showed better relief from sulpiride compared to paroxetine in patients having tested both drugs (P=.03). A similar difference was reflected in available headache scores (13 and 10 patients respectively; P=.03). Predominant side effects were sedation and depression, for paroxetine also nausea and head pain. None of the drugs improved headache more than one score-point on average. A placebo controlled trial of sulpiride may be warranted.     

A 12-week double-blind multi-centre study of paroxetine and imipramine in hospitalized depressed patients

Fifty-seven inpatients with major depression (DSM-III-R) entered a 12-week study comparing paroxetine and imipramine. Trends (not reaching statistical significance) in favour of paroxetine were seen on the Hamilton Depression Rating Scale (HDRS) and the Montgomery-Åsberg Depression Rating Scale (MADRS). The UKU Side Effect Rating Scale showed a significant difference in favour of paroxetine on reduced salivation. Global evaluation of side effect symptoms showed that significantly more paroxetine patients had no side effects, both in the investigators’ and the patients’ opinion. These results are in line with previous findings of paroxetine being an effective and well tolerated antidepressant.     

Paroxetine and imipramine in the treatment of depressive patients in psychiatric practice.

A total of 151 outpatients with endogenous or mixed endogenous and reactive depression were included in a 6-week double-blind study, with extension for up to 1 year, in psychiatric practice. The results showed trends in efficacy variables and a statistically significant difference in a benefit-risk ratio in favour of paroxetine (Seroxat, Paxil) compared with imipramine. Efficacy was largely maintained in both groups during long-term treatment. The frequency and severity of side effects in paroxetine patients declined markedly from short-term to long-term treatment, whereas changes in imipramine patients were less pronounced. Significantly more imipramine patients gained weight during long-term treatment. In conclusion, paroxetine is an effective and well tolerated antidepressant, well suited for outpatients in psychiatric practice.     

Paroxetine increases serum trimipramine concentration. A report of two cases

Paroxetine is a new antidepressant, a selective serotonin reuptake inhibitor (SSRI), which has marked inhibiting effect on microsomal cytochrome P450 enzymes in human liver. In this case report we describe two patients whose serum trimipramine and desmethyltrimipramine concentrations increased markedly when paroxetine was added to their drug therapy. We suggest that this was due to the inhibitory effect of paroxetine on the CYP 2D6-mediated metabolism of trimipramine. This interaction may be of clinical importance as both patients had side-effects, such as sedation and orthostatic hypotension, during the simultaneous administration.     

Altered brain activation pattern associated with drug-induced attenuation of enhanced depression-like behavior in rats bred for high anxiety.

BACKGROUND: The enhanced depression-like behavior in the forced swim test displayed by rats selectively bred for high anxiety-related behavior (HAB) as compared with their low anxiety counterparts (LAB) is abolished by chronic paroxetine treatment. The aim of the present study was to identify neuronal substrates underlying this treatment response in HABs. METHODS: The HAB rats received paroxetine (10 mg/kg/day) for 24 days via drinking water, and drug-induced modulation of neuronal activation patterns in response to forced swimming was mapped with the expression of the immediate early gene c-Fos as marker. RESULTS: Chronic paroxetine treatment reduced the immobility scores during forced swimming, confirming the previously observed antidepressant-like effect in these animals, and attenuated the forced swim-induced c-Fos response in a restricted set (11 of 70) of brain areas. These included limbic areas such as the prelimbic cortex, parts of the amygdala, the bed nucleus of the stria terminalis, dorsal hippocampus, dorsal lateral septum as well as hypothalamic and hindbrain areas (dorsolateral periaqueductal gray [PAG], locus coeruleus). Untreated LAB rats, which displayed low depression-like behavior comparable to that of treated HABs, also showed low swim stress-induced c-Fos response in most of these same areas, further supporting an association of attenuated neuronal excitability in the identified areas with attenuated depression-like behavior. CONCLUSIONS: These findings indicate that modulation of neuronal activation in a restricted set of defined, mainly limbic as well as selected hypothalamic and hindbrain areas by paroxetine treatment is associated with the reduction of enhanced depression-like behavior in a psychopathological animal model.     

Exposure to oral oxycodone is increased by concomitant inhibition of CYP2D6 and 3A4 pathways, but not by inhibition of CYP2D6 alone

AIM

The aim of this study was to find out whether the inhibition of cytochrome P450 2D6 (CYP2D6) with paroxetine or concomitant inhibition of CYP2D6 and CYP3A4 with paroxetine and itraconazole, altered the pharmacokinetics and pharmacological response of orally administered oxycodone.

METHODS

A randomized placebo-controlled cross-over study design with three phases was used. Eleven healthy subjects ingested 10 mg of oral immediate release oxycodone on the fourth day of pre-treatment with either placebo, paroxetine (20 mg once daily) or paroxetine (20 mg once daily) and itraconazole (200 mg once daily) for 5 days. The plasma concentrations of oxycodone and its oxidative metabolites were measured for 48 h, and pharmacological (analgesic and behavioural) effects were evaluated.

RESULTS

Paroxetine alone reduced the area under concentration–time curve (AUC(0,0–48 h)) of the CYP2D6 dependent metabolite oxymorphone by 44% (P < 0.05), but had no significant effects on the plasma concentrations of oxycodone or its pharmacological effects when compared with the placebo phase. When both oxidative pathways of the metabolism of oxycodone were inhibited with paroxetine and itraconazole, the mean AUC(0,∞) of oxycodone increased by 2.9-fold (P < 0.001), and its C_max by 1.8-fold (P < 0.001). Visual analogue scores for subjective drug effects, drowsiness and deterioration of performance were slightly increased (P < 0.05) after paroxetine + itraconazole pre-treatment when compared with placebo.

CONCLUSIONS

Drug interactions arising from CYP2D6 inhibition most likely have minor clinical importance for oral oxycodone if the function of the CYP3A4 pathway is normal. When both CYP2D6 and CYP3A4 pathways are inhibited, the exposure to oral oxycodone is increased substantially.     

固精汤结合帕罗西汀治疗早泄60例疗效分析

[目的]研究固精汤结合帕罗西汀对早泄（premature ejaculation, PE）的治疗效果。[方法]将2007年1月至2010年6月浙江省中医药大学附属第一医院泌尿外科就诊的早泄患者60例随机分为固精汤组和帕罗西汀组,每组30例。帕罗西汀组予以帕罗西汀10mg,口服,1次/晚;固精汤组在帕罗西汀组基础上加予固精汤,两组均治疗3个月。在入组前、治疗3个月后、停药后半年随访时使用计时和阴道内抽插次数两种方法评估的阴道内射精潜伏期（intravaginal ejaculation latency time, IELT）、中国早泄患者性功能评价表-5（CIPE-5）评价患者射精状态。[结果]治疗3个月后,两组患者IELT、抽插次数评分和CIPE-5评分均得以明显改善,而固精汤组改善更为明显。6个月后随访时固精汤组IELT、抽插次数评分及CIPE-5略有下降,但与治疗前相比,差异有统计学意义(P＜0.05),而帕罗西汀组各项指标则回至接近治疗前水平,与治疗前相比无明显差异(P＞0.05)。[结论]固精汤联合帕罗西汀,既能快速起效、增强患者自信心、改善性心理状态,又能提高远期疗效、避免停药后病情反复,能有效治疗PE。