Combination Of Nortriptyline Research Articles

ПОДАВЛЕНИЕ ПРОДУКЦИИ ПРОВОСПАЛИТЕЛЬНЫХ ЦИТОКИНОВ В ЕСТЕСТВЕННЫХ КИЛЛЕРАХ КРОВИ ПАЦИЕНТОВ С ХРОНИЧЕСКОЙ ОБСТРУКТИВНОЙ БОЛЕЗНЬЮ ЛЕГКИХ ПОД ВЛИЯНИЕМ НОРТРИПТИЛИНА

Aim. To determine the ability of nortriptyline, alone and in combination with budesonide, to inhibit the production of pro-inflammatory cytokines in the peripheral blood natural killer (NK) cells of patients with chronic obstructive pulmonary disease (COPD) and to establish the molecular mechanisms of the combined action of these drugs. Material and methods. Blood cells from COPD patients (n=21) were incubated with budesonide, nortriptyline, or their combination. Cytokine production, expression of glucocorticoid receptor β (GRβ), histone deacetylase 2 (HDAC2), and phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) in NK cells were analyzed by flow cytometry. Results. The combination of nortriptyline (10 μM) and budesonide (10 nM) reduced the synthesis of interleukin 4 (IL-4), IL-8, interferon γ, tumor necrosis factor α as well as the expression of GRβ and p-p38 MAPK in NK cells; it also increased the expression of HDAC2 more significantly than budesonide alone. Conclusions. Nortriptyline enhances the anti-inflammatory effect of budesonide by altering the expression of HDAC2, GRβ, p-p38 MAPK in peripheral blood NK cells of patients with COPD. The data obtained indicate the advisability of combining nortriptyline with budesonide for the treatment of COPD.

Nortriptyline Modulates the Migration of Peripheral Blood Lymphocytes and Monocytes in Patients with Chronic Obstructive Pulmonary Disease.

In the present study, the effect of nortriptyline (1 and 10 μM), budesonide (10 nM) and their combination on the migration of peripheral blood lymphocytes and monocytes from patients with chronic obstructive pulmonary disease (COPD) towards chemokines CCL5 and CXCL10 was evaluated by flow cytometry. Nortriptyline (10 μM), both alone and in combination with budesonide, inhibited the migration of T helper cells, cytotoxic T lymphocytes, NK cells and B lymphocytes towards CCL5 and CXCL10, as well as enhanced monocyte migration towards these chemokines. The combination of nortriptyline (1 μM) and budesonide suppressed the chemotaxis of lymphocyte subpopulations towards CXCL10, but not towards CCL5, more effectively than budesonide alone. The combination of nortriptyline (10 μM) and budesonide inhibited the migration of lymphocyte subpopulations towards CCL5 and CXCL10 and activated monocyte chemotaxis towards both chemokines more effectively than budesonide alone. The results of this study demonstrate the ability of nortriptyline alone to modulate the migration of peripheral blood lymphocytes and monocytes from patients with COPD and to potentiate the effects of budesonide.

Nortriptyline overcomes corticosteroid resistance in NK and NKT-like cells from peripheral blood of patients with chronic obstructive pulmonary disease

Introduction: An antidepressant nortriptyline potentiates glucocorticoid (GC) action with synergistic suppression of inflammatory mediator release, but the precise molecular mechanism is unknown.
 Materials and methods: Peripheral blood cells from patients with chronic obstructive pulmonary disease (COPD) (n = 21) were incubated with nortriptyline (1 μM or 10 μM), budesonide (10 nM), or their combinations, followed by stimulation with phorbol myristate acetate (PMA) and ionomycin. Cytokine production, glucocorticoid receptor β (GRβ), histone deacetylase 2 (HDAC2) and histone H4 acetylation of K8 (HAT) expression, p65 NF-kB and p38 mi­togen-activated protein kinase (p38 MAPK) phosphorylation in NK (CD3-CD56+) and NKT-like (CD3+CD56+) cells were analyzed by flow cytometry.
 Results: We observed that nortriptyline (10 μM) significantly attenuated the effects of PMA/ionomycin on the synthe­sis of interferon γ (IFNγ), interleukin 4 (IL-4), and IL-8, expression of GRβ and HAT, as well as p65 NF-kB and p38 MAPK phosphorylation in NK and NKT-like cells, whereas nortriptyline (1 μM) only inhibited IL-4 production by NK and NKT-like cells.
 Discussion: The combination of nortriptyline (10 μM) and budesonide decreased IFNγ, tumor necrosis factor α, IL-4, IL-8, and GRβ expression, as well as phosphorylated p38 MAPK and p65 NF-κB levels by NK and NKT-like cells above that of budesonide alone. Furthermore, the same association of drugs enhanced HDAC2 expression in NK and NKT-like cells.
 Conclusion: Collectively, our results show that nortriptyline might enhance GC function through modulation of HAT, HDAC2, GRβ, phospho-p38 MAPK expression. These data provide a strong rationale for combining nortriptyline with budesonide to treat COPD.

Adjuvant Migraine Medications in the Treatment of Sudden Sensorineural Hearing Loss.

To examine the hearing outcomes of patients with sudden sensorineural hearing loss (SSNHL) treated with oral and intratympanic (IT) steroid only or a combination of steroid and migraine treatment. Our hypothesis was that adjuvant migraine medications may improve outcomes in SSNHL. A retrospective chart review at a tertiary otology center was conducted to identify patients with SSNHL who received oral steroid and IT dexamethasone injection(s) with or without migraine medications (a combination of nortriptyline and topiramate). A total of 47 patients received oral steroid and IT dexamethasone injection(s) only, and 46 patients received oral steroid and IT dexamethasone injection(s) as well as migraine lifestyle changes plus a combination of nortriptyline and topiramate. There were no significant differences in demographics and baseline audiometric data between the two groups. Both groups demonstrated improvements in pure tone average (PTA) and hearing thresholds at 250 Hz and 8000 Hz posttreatment. However, compared to steroid-only group, the adjuvant migraine medications group had significantly greater improvements in hearing thresholds at the lower frequencies (250 Hz, 500 Hz, 1000 Hz). Patients in the latter cohort also had greater improvement in PTA (P = .01) and received fewer IT injections (P = .04) PTA improvement of ≥ 10 dB was observed in 36 patients (78%) in the adjuvant migraine medications group and 22 patients (46%) in the control group (P < .001). In multimodal treatment of SSNHL, supplementing oral and IT steroid with migraine medications may result in greater improvements in lower frequency hearing thresholds and PTA. Furthermore, adjuvant migraine treatment can lead to decrease in number of IT injections, thus reducing procedure-related risks and complications. 3 Laryngoscope, 131:E283-E288, 2021.

Effect of sertraline on plasma nortriptyline levels in depressed elderly.

Several serotonin selective reuptake inhibitors have been reported to be inhibitors of the cytochrome P450 2D6 (CYP2D6). Thus, they may increase the plasma level of secondary amine tricyclic antidepressants, which are predominantly metabolized through this enzyme. Except for a few case reports, no clinical data document the degree of this drug-drug interaction in elderly depressed patients. We systematically examined this interaction by determining the change in plasma nortriptyline levels in 14 elderly depressed patients in whom sertraline was added to nortriptyline. After addition of 50 mg/day of sertraline, the median increase in plasma nortriptyline level over baseline was 2% (range, -26% to 117%; p = .30). In 2 patients (14%), there was an increase of 50% or more. For patients taking higher sertraline doses (N = 7; 100 or 150 mg/day), the median increase in plasma nortriptyline level over baseline was 40% (range, -12% to 239%; p = .08). Overall, a modest effect of sertraline was observed on nortriptyline metabolism in these elderly depressed patients. This is consistent with prior reports of a weak inhibition of CYP2D6 by sertraline in vitro and in young healthy volunteers. However, some patients showed a change in plasma nortriptyline level that would be considered clinically significant. Thus, careful monitoring of plasma nortriptyline levels is recommended in all patients treated with a combination of nortriptyline and sertraline.

Time to remission in late‐life depression: Analysis of effects of demographic, treatment, and life‐events measures

AbstractThis study examined elderly patients being treated with a combination of nortriptyline and interpersonal psychotherapy to determine what demographic, clinical, illness‐history, and treatment‐parameter variables might predict rate of remission of the index episode. The 115 patients, aged 60 to 80 years, were suffering from at least their second lifetime episode of major depression (unipolar, nonpsychotic). Proportional hazards modeling (univariate and multivariate) showed that 4 of the 28 variables examined were significant in predicting a slower rate of response to treatment: 1) the presence of a stress‐provoking agent, such as a severely threatening life event or an ongoing major difficulty during the 6 months before onset of the index episode, 2) eccentric cluster personality features (i.e., paranoid, schizoid, and schizotypalpersonality pathologies), 3) a low level of tangible social support, and 4) earlier age at first episode. Median time to remission was increased by 2.5 weeks (from 6.5 to 9 weeks) in the presence of a stress‐provoking agent. The final model retained two variables (the presence of a stress‐provoking agent and perception of diminished social support) as significantly predictive of prolonged time to remission. Thus, these findings suggest a somewhat longer expected time to response among patients with negative psychosocial circumstances. We speculate that the use of psychotherapy and/or other adjunctive pharmacotherapy may be critical to earlier successful treatment outcome in such patients. Depression 1:250–256 (1993). © 1993 Wiley‐Liss, Inc.