|Year : 2016 | Volume
| Issue : 1 | Page : 22-26
Desipramine plus levocetirizine as a treatment for persistent allergic rhinitis
Diaa El Din Mohamed El Hennawi1, Mohamed Rifaat Ahmed MD 1, Ashraf Saad Abou-Halawa1, Wael Abdelkafy1, Ahmed Geneid2
1 Department of Otolaryngology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt
2 Department of Otorhinolaryngology and Phoniatrics-Head and Neck Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
|Date of Submission||01-Jan-2016|
|Date of Acceptance||16-Feb-2016|
|Date of Web Publication||26-Jul-2016|
Mohamed Rifaat Ahmed
Department of Otolaryngology, Faculty of Medicine, Suez Canal University, Ismailia
Source of Support: None, Conflict of Interest: None
Persistent allergic rhinitis has significant effects on the quality of life (QOL), especially on sleep and work performance, and is associated with specific psychiatric syndromes.
The aim of the present study was to verify the efficacy of combined desipramine and levocetirizine in the treatment of psychological stress related to persistent allergic rhinitis, and to thereby improve the QOL of the patient.
Patients and methods
A total of 132 psychologically stressed persistent allergic rhinitis patients (positive Kessler Psychological Distress Scale scores ≥12) were randomly divided into two groups: the control group, which received levocetirizine, and the study group, which received levocetirizine plus desipramine. QOL for all patients was assessed by using a seven-point scale after the treatment period.
There was a highly statistically significant better QOL in the study group (6.79) compared with the control group (2.21) (t-test=15.17 and P = 0.0001).
Desipramine and levocetirizine have a better effect on the QOL outcomes in the treatment of patients with persistent allergic rhinitis, and having psychological stress disorders.
Level of evidence: 3b.
Keywords: allergic, desipramine, levocetirizine, psychological stress, quality of life, rhinitis
|How to cite this article:|
El Hennawi DE, Ahmed MR, Abou-Halawa AS, Abdelkafy W, Geneid A. Desipramine plus levocetirizine as a treatment for persistent allergic rhinitis. Pan Arab J Rhinol 2016;6:22-6
|How to cite this URL:|
El Hennawi DE, Ahmed MR, Abou-Halawa AS, Abdelkafy W, Geneid A. Desipramine plus levocetirizine as a treatment for persistent allergic rhinitis. Pan Arab J Rhinol [serial online] 2016 [cited 2017 Sep 24];6:22-6. Available from: http://www.PAJR.eg.net/text.asp?2016/6/1/22/183736
| Introduction|| |
Persistent allergic rhinitis has a significant effect on quality of life (QOL), especially on sleep and work performance .
Allergic rhinitis classification actually reflects the clinical course with its burden on QOL into: intermittent (total duration <4 weeks) or persistent (symptoms continue throughout the whole year); according to severity, it is classified as follows: either mild (patients are generally able to sleep normally and perform normal activities) or moderate/severe (significantly affects sleep and daily activities) .
A strong relationship between persistent allergic rhinitis and specific psychiatric syndromes has been illustrated in many studies .
In their studies, Katotomichelakis et al.  mentioned a 1.7 times higher psychological stress symptoms in persistent allergic rhinitis patients; in addition, Garg and Silverberg  found a higher rate of panic disorder with major depression symptoms among the same population.
Many theories demonstrate these relationship as either immune-related illnesses  through the presence of cytokines ; sleep disruption with subsequently negative effects on psychiatric symptoms ; or genetic risk between both allergies and depression .
Levocetirizine (5 mg/day) is a potent H1-receptor antagonist with proven efficacy as a therapeutic option in persistent allergic rhinitis improving the nasal symptoms, and thereby improves significantly the impaired QOL .
Desipramine is a tricyclic antidepressant, beside its indication for the treatment of depression and improve patients mood; it has antihistaminic properties, affecting histamine H1 receptors by regulating Treg and Th17 cells ,.
The present study aimed to verify the efficacy of combined dose of desipramine and levocetirizine in the treatment of psychological stress-persistent allergic rhinitis and thereby improve QOL outcomes.
| Patients and Methods|| |
Design, setting and participants
A double-blinded, randomized clinical trial was conducted in the Otolaryngology Department, Suez Canal University Hospital (Ismailia, Egypt), from December 2008 to June 2011. The study protocol was approved by the local ethics committee, and written informed consent was obtained from all patients.
Inclusion and exclusion criteria
A total of 132 psychologically stressed persistent allergic rhinitis patients (longer than 4 days/week and for >4 consecutive weeks)  and positive to Kessler Psychological Distress Scale scores of greater than or equal to 12 were included in our study. Kessler Psychological Distress Scale scores demonstrate the responses to the K5 questions with a minimum possible score of 5 and a maximum possible score of 25. Low scores, 5–11, indicate negative psychological distress and high scores, 12–25, indicate positive psychological distress .
In contrast, patients negative to Kessler Psychological Distress Scale scores (5–11), with rhinitis medicamentosa, receiving drugs known to induce nasal obstruction (e.g. β-blockers), and with previous nasal surgery, hormonal therapy, pregnancy, lactation, occupational dust exposure, nasal polyposis, or rhinosinusitis, were excluded from the study population.
All patients were subjected to complete history taking including allergic rhinitis symptoms assessment using the visual analogue scale (VAS), which assesses subjective symptoms, with 0 indicating no symptoms and10 indicating severe and/or constant symptoms.
A complete ENT examination, with rigid nasal endoscopic examinations (Hopkins II Endoscope; Karl Storz, Tuttlingen, Germany), paranasal sinus computed tomography scan, and skin prick test, was carried out.
Psychological evaluation of Kessler Psychological Distress Scale scores demonstrates the responses to the 25 questions, with a minimum possible score of 5 and a maximum possible score of 25. Low scores, 5–11, indicate negative psychological distress (who were excluded from the study) and high scores, 12–25, indicate positive psychological distress (who were included in the study) .
Patients were randomly divided into the study and the control group using a blocked randomization scheme by using computer-generated random numbers.
The control group received levocetirizine (5 mg/day)  for 30 days and the study group received levocetirizine (5 mg/day) plus desipramine (25 mg/day) for the same period of time .
Outcome measurement assessment
The primary outcome was the effect of treatment on QOL after 30 days from treatment initiation using a seven-point scale for assessing severity of allergic rhinitis on sleep pattern at night, work performance, and social and/or recreational activities .
Data collected were processed using SPSS (version 23; SPSS Inc., Chicago, Illinois, USA). Quantitative data were expressed as means±SD, whereas qualitative data were expressed as numbers and percentages. Student's t-test was used to compare the significance of difference for quantitative variables that followed a normal distribution.
Written informed consent was obtained from all patients. The local ethics committee approved the study.
| Results|| |
Out of a total of 132 psychological stressed persistent allergic rhinitis patients, with a mean age of 41.2 ± 6.8 years [81 (61.4%) women and 51 (38.6%) men], included in the study, 113 (85.6%) patients showed the main symptoms of sneezing, followed by itchy nose in 95 (71.9%) patients, nasal obstruction in 82 (62.1%), patients and watery rhinorrhea in 79 (59.8%) patients, whereas the main finding during nasal examination was pale, congested, bluish mucosa in 115 (87.1%) patients.
Patients were divided randomly into two equal groups: the control group (n = 66) received levocetirizine (5 mg/day) for 30 days; and the study group (n = 66) received levocetirizine (5 mg/day) plus desipramine (25 mg/day) for the same period of time.
The mean intensity of nasal symptoms according to VAS before treatment in the control group was sneezing 9.35, whereas it was 9.09 in the study group: nasal obstruction was 9.13 and 8.98, respectively; watery rhinorrhea was 7.97 and 8.06, respectively; and, finally, itchy nose was 7.43 and 7.81, respectively, without any statistically significance difference between the two groups ([Table 1]).
|Table 1 Mean degree of different allergic nasal symptoms before treatment in both groups, for those who were positive on the Kessler Psychological Distress Scale scores|
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After 30 days, the mean intensity of nasal symptoms according to VAS in the control group was sneezing 3.91, whereas it was 1.08 in the study group, nasal obstruction was 4.26 and 1.21, respectively; watery rhinorrhea was 4.92 and 1.01, respectively, and itchy nose was 3.24 and 1.57, respectively. There was highly statistically significant improvement in the allergic nasal symptoms of the study group (receiving levocetirizine plus desipramine) compared with the control group (only levocetirizine) ([Table 2]).
|Table 2 Mean degree of different allergic nasal symptoms after treatment in both groups, for those who were positive on the Kessler Psychological Distress Scale scores|
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QOL scalewas calculated, and the assessment at the end of the treatment revealed a highly significantly better life quality for the study group (6.79) compared with the control group (2.21) (t-test=15.17 and P = 0.0001), as according to the QOL scale, 1–2 means poor QOL, 3–4 fair QOL, 5–6 average QOL, and seven means good QOL. Overall, 87.9% patients in the study group reported a good QOL scale score compared with only 4.5% in the control group, with a high statistically significant difference ([Table 3] and [Figure 1]).
|Table 3 Quality of life scale assessment after treatment in both groups, for those who were positive on the Kessler Psychological Distress Scale scores|
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|Figure 1: Quality of life scale assessment after treatment in both groups, for participants who were positive on the Kessler Psychological Distress Scale scores.|
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| Discussion|| |
Persistent allergic rhinitis is a common disease with significant burden on the QOL. Many treatment options directed at symptomatic relief are available, but sometimes the traditional treatment is not effective to address all aspects of the disease burden .
Allergic rhinitis is the sixth most prevalent chronic condition in the world, with a high risk for developing chronic rhinosinusitis, otitis media with effusion, nasal polyposis, and bronchial hyperactivity, which usually had a great burden on QOL .
Many authors have investigated the mechanism of psychological stress producing persistent allergic rhinitis, suggesting that neuropeptides and hormones released result in immune-mediated and neurogenic inflammatory processes, with deregulation of normal haemostatic neural, endocrine systems leading to an increase in the expression of the disease symptoms ,,,.
In their study, Tomljenovic et al.  mentioned a strong relationship between changes in allergy symptom scores and changes in depression scores leading to a larger negative recurrent mood disorders in patients with atopy and allergic rhinitis.
Lind et al.  mentioned in their study that there is an associated relationship between the psychological and immunological state in patients with atopy as they are more depressive, and complain of anxiety, with psychosomatic symptoms.
The control group received levocetirizine for 30 days while the study group received levocetirizine plus desipramine for the same period of time. There was marked highly statistically significantly allergic nasal symptoms improvement in the study group.
Allergic rhinitis associated with depression is recognized with recommendation to treat the depression, but fortunately, desipramine has double action; beside being a tricyclic antidepressant agent, it is also attenuating to the allergic nasal symptoms by antiallergic action, as found by Zhang et al.  in a study on allergic rhinitis mice.
Rao et al.  recognized suppression of cutaneous histamine-induced wheal-and-flare with desipramine.
In addition, there was a highly significantly better life quality in the study group (6.79) compared with the control group (2.21) (t-test=15.17 and P = 0.0001) at the end of the treatment period.
Patients with persistent allergic rhinitis usually from poor QOL scores. Such poor QOL probably results from a number of symptoms like difficulty getting to sleep, waking up during the night, fatigue, mood changes irritability, memory deficits, and lack of a good night's sleep as a result of their persistent nasal symptoms. That result in forming a burden their daily life, which limits them from doing well in their work .
Good QOL was reported in 87.9% patients in the study group, whereas in the control group it was only in 4.5%. Meanwhile, poor QOL was not reported in the study group; it was reported by 36.4% participants in the control group.
It should be noted that the concept of QOL differs between individuals depending on the degree of expectations and perceptions of the disease. Accordingly, it varies principally depending on the standards of the individual regards 'personal well-being', perception of the surrounding world, and expectations regarding treatment .
The QOL of allergic rhinitis patients was often impaired, not only due to the typical symptoms of the disease (sneezing, pruritus, nasal obstruction, and rhinorrhea) but also due to the activity of the mediators such as histamine, leukotrienes (C4 and D4), interleukins (ILs) (IL-1β, IL-4, IL-5 and IL-13), prostaglandin D2, substance P, and bradykinin, which participate in its pathophysiology and can disrupt sleep .
Unfortunately, a great burden associated with persistent allergic rhinitis goes beyond the impairment of social and physical functioning; this component is rarely recognized or valued when the treatment is usually prescribed with a possible causal factor of comorbidities such as asthma and sinusitis .
We did not aim to point to a specific new treatment regimen for persistent allergic rhinitis, but our raw data showed better results for the study group, which received desipramine plus levocetirizine, compared with the control group, which received levocetirizine alone.
Finally, we want to point to the fact that persistent allergic rhinitis patients do not respond to traditional antiallergic treatment; psychosocial stresses could be a strong etiological factor. If properly treated, the patients' QOL could be improved.
| Conclusion|| |
A combination of desipramine plus levocetirizine has a better QOL outcomes in the treatment of patients with persistent allergic rhinitis having psychosocial stresses disorders.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Bozek A, Ignasiak B, Kasperska-Zajac A, Scierski W, Grzanka A, Jarzab J. Local allergic rhinitis in elderly patients. Ann Allergy Asthma Immunol 2015; 114(3):199–202.
Braido F, Arcadipane F, Marugo F, Hayashi M, Pawankar R. Allergic rhinitis: current options and future perspectives. Curr Opin Allergy Clin Immunol 2014; 14:168–176.
Sanna L, Stuart AL, Pasco JA, Jacka FN, Berk M, Maes M, et al.
Atopic disorders and depression: findings from a large, population-based study. J Affect Disord 2014; 155:261–265.
Katotomichelakis M, Simopoulos E, Tzikos A, Balatsouras D, Tripsianis G, Danielides G, et al.
Demographic correlates of anxiety and depression symptoms in chronic sinonasal diseases. Int J Psychiatry Med 2014; 48(2):83–94.
Garg N, Silverberg JI. Association between childhood allergic disease, psychological comorbidity, and injury requiring medical attention. Ann Allergy Asthma Immunol 2014; 112(6):525–532.
Coban H, Aydemir Y. The relationship between allergy and asthma control, quality of life, and emotional status in patients with asthma: a cross-sectional study. Allergy Asthma Clin Immunol 2014; 10(1):67.
Yang P, Gao Z, Zhang H, Fang Z, Wu C, Xu H, Huang QJ. Changes in proinflammatory cytokines and white matter in chronically stressed rats. Neuropsychiatr Dis Treat 2015; 11:597–607.
Ridolo E, Caffarelli C, Olivieri E, Montagni M, Incorvaia C, Baiardini I, Canonica GW. Quality of sleep in allergic children and their parents. Allergol Immunopathol (Madr) 2015; 43(2):180–184.
Wamboldt MZ, Hewitt JK, Schmitz S, Wamboldt FS, Räsänen M, Koskenvuo M, et al.
Familial association between allergic disorders and depression in adult Finnish twins. Am J Med Genet 2000; 96(2):146–153.
Mullol J, Bachert C, Bousquet J. Management of persistent allergic rhinitis: evidence-based treatment with levocetirizine. Ther Clin Risk Manag 2005; 1(4):265–271.
Rao KS, Menon PK, Hilman BC, Sebastian CS, Bairnsfather L. Duration of the suppressive effect of tricyclic antidepressants on histamine-induced wheal-and-flare reactions in human skin. J Allergy Clin Immunol 1988; 82(Pt 1):752–757.
Zhang Y, Zhen H, Yao W, Bian F, Mao X, Yang X, Jin S. Antidepressant drug, desipramine, alleviates allergic rhinitis by regulating Treg and Th17 cells. Int J Immunopathol Pharmacol 2013; 26(1):107–115.
Solelhac G, Charpin D. Management of allergic rhinitis. F1000Prime Rep 2014; 6:94.
Anderson TM, Sunderland M, Andrews G, Titov N, Dear BF, Sachdev PS. The 10-item Kessler Psychological Distress Scale (K10) as a screening instrument in older individuals. Am J Geriatr Psychiatry. 2013; 21(7):596–606.
Burckhardt CS, Anderson KL. The Quality of Life Scale (QOLS): reliability, validity, and utilization. Health Qual Life Outcomes 2003; 1:60.
Scadding GK. Optimal management of allergic rhinitis. Arch Dis Child 2015; 100(6):576–582.
Thompson A, Sardana N, Craig TJ. Sleep impairment and daytime sleepiness in patients with allergic rhinitis: the role of congestion and inflammation. Ann Allergy Asthma Immunol 2013; 111(6):446–451.
Baran H, Ozcan KM, Selcuk A, Cetin MA, Cayir S, Ozcan M, Dere H. Allergic rhinitis and its impact on asthma classification correlations. J Laryngol Otol 2014; 128(5):431–437.
Kim SH, Mun SJ, Han DH, Kim JW, Kim DY, Rhee CS. Three-year follow-up results of sublingual immunotherapy in patients with allergic rhinitis sensitized to house dust mites. Allergy Asthma Immunol Res 2015; 7(2):118–123.
Walter Canonica G, Bousquet J, Van Hammée G, Bachert C, Durham SR, Klimek L, et al
. XPERT Study Group. Levocetirizine improves health-related quality of life and health status in persistent allergic rhinitis. Respir Med 2006; 100(10):1706–1715.
Liezmann C, Klapp B, Peters EM. Stress, atopy and allergy: a re-evaluation from a psychoneuroimmunologic perspective. Dermatoendocrinol 2011; 3(1):37–40.
Tomljenovic D, Pinter D, Kalogjera L. Perceived stress and severity of chronic rhinosinusitis in allergic and nonallergic patients. Allergy Asthma Proc 2014; 35(5):398–403.
Lind N, Nordin M, Palmquist E, Nordin S. Psychological distress in asthma and allergy: the Västerbotten Environmental Health Study. Psychol Health Med 2014; 19(3):316–323.
Meltzer EO, Gross GN, Katial R, Storms WW. Allergic rhinitis substantially impacts patient quality of life: findings from the Nasal Allergy Survey Assessing Limitations. J Fam Pract 2012; 61(Suppl):S5–10.
Schoenwetter WF, Dupclay L Jr, Appajosyula S, Botteman MF, Pashos CL. Economic impact and quality-of-life burden of allergic rhinitis. Curr Med Res Opin 2004; 20(3):305–317.
Boghdadi G, Hammad N, Amer A, Sammour S, Sorour S. R848, a Toll-like receptors 7 and 8 agonist, a potential therapy for allergic rhinitis patients. Inflamm Allergy Drug Targets 2014; 13(2):144–149.
Small M, Piercy J, Demoly P, Marsden H. Burden of illness and quality of life in patients being treated for seasonal allergic rhinitis: a cohort survey. Clin Transl Allergy 2013; 3(1):33.
[Table 1], [Table 2], [Table 3]