University Psychiatric Hospital Ljubljana, Studenec 48, SI-1260 Ljubljana Polje, Slovenia
Korespondenca/ Correspondence:
doc. dr. Virginija Novak Grubič, dr. med., Psihiatrična klinika Ljubljana, Center za klinično psihiatrijo University Psychiatric Hospital Ljubljana, Studenec 48, SI-1260 Ljubljana Polje, Slovenia Tel: +386 1 5872149 Fax: 00386 1 5283 737 e-mail: virginija.novak@ psih-klinika.si
Ključne besede:
hospitalizirani bolniki, akutna depresivna epizoda, telesni bolečinski simptomi, VAS
Key words:
hospitalized patients, acute depressive episode, painful physical symptoms, VAS
Citirajte kot/Cite as:
Zdrav Vestn 2013; 82: 93-8
Prispelo: 1. mar. 2012, Sprejeto: 27. dec. 2012
Painful physical symptoms in hospitalized patients with acute depressive episode: results from a naturalistic study
Telesni bolečinski simptomi pri hospitaliziranih bolnikih z akutno epizodo depresije: rezultati naturalistične raziskave
Rijavec Nikolina, Novak Grubič Virginija
Abstract
Background: Depressive symptoms in patients with chronic pain (organic or functional) are well recognized. However, studies on pain were mostly conducted in non-psychiatric settings, and there is a paucity of data on painful physical symptoms (PPS) in patients with depression, especially in acute depressive episode (ADE). The aim of the study was to find out the prevalence of PPS in patients with ADE and to compare socio-demographic and clinical variables in patients with and without PPS.
Methods: 150 somatically healthy patients, hospitalized due to ADE were screened for PPS. Data on PPS location and severity, basic socio-demographic characteristics, illness severity, therapy, suicidality, and comorbid alcohol abuse were collected.
Results: 71 % of patients with ADE reported at least one painful physical symptom. Headache was the most common complaint. Patients with PPS had more severe depressive symptoms, lower level of functioning, and were prescribed more analgesics. However, no differences in so-cio-demographic characteristics, antidepressant therapy, suicidality or alcohol dependence were found.
Conclusions: The results show high prevalence of PPS in somatically healthy hospitalized patients with ADE and partly concur with results from similar studies. The high use of analgesics in patients with depression and painful physical symptoms opens the issue of rational pharmaco-therapy.
Izvleček
Izhodišča: Depresivni simptomi so pri bolnikih s kronično bolečino pogosti in dobro poznani. Raziskave o bolečinskih simptomih in soobo-levnosti z depresijo so bile večinoma opravljene zunaj psihiatričnega področja. Raziskav znotraj psihiatrije o telesnih bolečinskih simptomih (TBS) pri bolnikih z depresijo, posebno z akutno depresivno epizodo (ADE), je malo. Z raziskavo smo želeli ugotoviti pojavnost TBS pri bolnikih z ADE ter primerjati klinične dejavnike bolnikov z depresijo s TBS in brez nje.
Metode: Pri 150 telesno zdravih bolnikih, ho-spitaliziranih z diagnozo ADE, smo ugotavljali prisotnost TBS. Zbrali smo podatke o mestu in jakosti TBS, osnovnih socialno-demografskih značilnostih, izraženosti depresije, zdravljenju, samomorilnosti in morebitni odvisnosti od alkohola.
Rezultati: 71 % bolnikov je navajalo vsaj en bolečinski simptom, med katerimi je bila najpogostejša pritožba glavobol. Bolniki s TBS so imeli bolj izražene simptome depresije in so imeli predpisanih več protibolečinskih zdravil. Med bolniki z ADE in s TBS ter bolniki z ADE brez TBS nismo ugotovili razlik glede na socialno--demografske značilnosti, antidepresivno zdravljenje, samomorilnost in odvisnost od alkohola.
Zaključki: Rezultati raziskave so pokazali visoko pojavnost TBS pri telesno zdravih bolnikih, ho-spitaliziranih zaradi ADE, kar se delno ujema z izsledki podobnih tujih raziskav. Ugotovili smo pogosto in intenzivno uporabo protibolečinskih zdravil pri bolnikih z depresijo in TBS, kar odpira vprašanje racionalne farmakoterapije.
Introduction	psychiatry, and in most of the studies the
population of patients is diverse while the
People with organic or functional painful	origin of pain (functional vs. organic) is po-
conditions become depressed in up to 80 »/o.1	orly defined. However, the co-occurrence of
On the other hand, about 50 % of depressed	pain and depression might be attributed to
patients report pain.	common neurobiological and psychological
There is a large body of evidence that pa-	causes. 6 The presence of PPS complicates
tients with depression often complain of dif-	the recognition and treatment of depressi-
ferent somatic symptoms, among them po-	on and is associated with worse depression
orly defined painful conditions.3 However	outcomes.7-9 PPS often represent residual there is still a lack of consistent terminology	symptoms and are a risk factor for relapse of which probably reflects conceptual issues	depression.10 Opioid analgesics are an effec-about the nature of pain and depression.2	tive treatment option for pain control althoT° define pain symptoms in depressed pa-	ugh there are safety concerns about abuse tients different expressions appear in the li-	and dependence risk. Tramadol was shown terature. Terms like "functional", "medically	to have antidepressant efficacy" while an-unexplained", "unexplained painful physical	tidepressants and anticonvulsants might be symptoms" or "psychosomatic" are the most	adjuvant analgesic agents alone or in combi-
commonly used.	nation with psychotherapy for treatment of
The published data show that clinici-	depression with PPS 12-15
ans meet patients with painful physical	The primary objective of our study was
symptoms (PPS) with or without depressi-	to identify the prevalence of PPS in otherwi-
on in different clinical settings, often non-	se somatically healthy patients hospitalized
-psychiatric. There is a paucity of data on	in Psychiatric intensive care unit due to
depression with pain in patients treated in	acute depressive episode (ADE), and to me-
Table 1: comparison of patients with depression and PPS and with depression without PPS (N=150)
	DEP with PPS (N=107)	DEP without PPS (N=43)	X2, U	p
Gender(%)	M 35 (32.72) F 72 (67.28)	M 17 (39.53) F 26 (60.47)	0.631*	0.427
Age (years, SD)	50.14 (± 11.44)	50.77 (± 12.59)	2262.500**	0.874
No. of previous hospitalizations (SD)	4.81 (± 5.92)	4.56 (± 6.11)	2160.500**	0.553
HAM-D score (SD)	32.91 (± 5.76)	28.79 (± 5,98)	1424.000**	< 0.001
ZUNG score (SD)	60.90 (± 8.24)	56.14 (± 9.98)	1588.000**	0.003
cgi-s (SD)	5.55 (± 0.75)	4.72 (± 0.76)	1073.000**	< 0.001
gas (SD)	33.10 (± 12.57)	47.40 (± 10.69)	899.500**	< 0.001
alcohol use disorder N (%)	17 (15.88)	5 (11.62)	0.879*	0.644
Analgesic use N (%) ►	parcetamol and NSAIDs N (%) ►	tramadol N (%)	35 (32.71) 32 (29.90) 3 (2.80)	2 (4.65) 2 (4.65) 0 (0.00)	13.026*	0.001
Previous anxiolytic use N (%)	57 (53.27)	13 (30.23)	6.541*	0.011
SNRIs prescribed N (%)	86 (80.37)	37 (86.04)	0.669*	0.413
Anticonvulsants prescribed N (%)	33 (30.80)	14 (32.57)	0.459*	0.795
History of attempted suicide N (%)	63 (58.87)	24 (55.81)	2.202*	0.821
* = x2 (chi square test) ** = U (Mann-Whitney test)
Figure 1: Distribution of painful physical symptoms by location (n=i07)
asure the intensity and location of painful symptoms. The secondary objective was to evaluate the possible differences in socio--demographic and illness related variables, including pharmacotherapy, in patients with and without PPS. We hypothesized that there was a difference in socio-demographic and illness-related factors between patients with depression with and without PPS. The study was conducted in naturalistic conditions.
Patients and Methods
Patients, hospitalized in the Psychiatric Intensive Care Unit of the University Psychiatric Hospital in Ljubljana, Slovenia, under the diagnosis of ADE (ICD - 10 criteria for recurrent severe depressive episode, with or without psychotic symptoms) were consecutively recruited over a two-year period. The inclusion criteria were both genders, age 18 to 65 years, and the absence of co-morbid somatic illness that would require diagnostics or somatic treatment. Patients with chronic conditions like diabetes mellitus, chronic organic pain due to orthopedic or neurological condition or pathological laboratory findings were excluded. Patients were interviewed in the first week after admission. Depression was evaluated with 21-item Hamilton Depression Scale (HAM-D), Cli-
nical Global Impression-Severity (CGI-S), General Assessment Scale (GAS) and Zung Questionnaire.16-19 Painful symptoms were checked for location (head, chest, abdomen, spine, arms and legs) and severity with Visual Analogue Scale (VAS: 1-10). Data on basic socio-demographic characteristics, history of suicide attempt, co-morbid alcohol abuse, and prescribed pharmacotherapy were also collected.
All participants gave informed consent.
Statistical analysis
Patients were divided into two groups: one with and the other without PPS, and compared. ^2 test for categorical variables was used. Due to the non-Gaussian distribution of variables on age, VAS, CGI-S, HAM--D and Zung Questionnaire, non-parametric Mann-Whitney U test was used. P< 0.05 was considered statistically significant. Data were analyzed with SPSS version 17.0.
Results
Data from 150 patients were collected (47 (32 %) male). 107 (71 %) patients reported painful symptoms: 26.1 % had one painful symptom, 34.6 % two, and 39.3 % three or more. The mean severity of PPS was between 6 to 7 on VAS for all locations with headache
being the most common. The distribution of PPS is presented in Figure 1.
There were no statistical differences in socio-demographic characteristics between both groups (p> 0.05). 52.3 % of patients with depression and PPS were employed (41.9 % of patients with depression without PPS) and 50.5 % had high school education vs. 48.8 %, respectively. 65.4 <% of depressed patients with PPS were married vs. 51.2 % in the group of patients without PPS. However, differences in illness related variables were found. Patients with depression and PPS scored higher on all clinical scales, and were more often prescribed anxiolytics before hospitalization while one third of these patients received analgesics (29.9 % recived paracetamol and non steroid antiinflammatory drugs (NSAID), while 2.8 % received tramadol, respectively). The results are presented in Table 1.
Discussion
There is not much data on hospitalized patients with ADE and PPS in the literature. The majority of studies recruited non-acute outpatients, often in primary care or in other settings and did not explicitly exclude somatically ill patients.
In our study patients were carefully selected and only somatically healthy patients with ADE were included. Without other medical explanation, PPS were considered to be part of somatic syndrome of depression.
In comparison to other studies, high prevalence of PPS was found in our patients. In other studies in psychiatric setting the prevalence of PPS was between 30.4 % to 69 % in patients with major depressive disorder.20-22 In a study by Arnow, patients with major depression reported significantly higher proportion of chronic pain than those without depression (66 % versus 43 %).23 Patients with PPS were generally older and of female gender. In our sample, patients were almost the same age in both groups, with two thirds of females among patients with depression and PPS.
Among PPS headache was the most common complaint. Our results concur with a recent study where 68 % of outpatients with
major depression reported PPS, 43 % had one or two symptoms with headache being the most common.22
In a multicenter international study STAR*D (Sequenced Treatment Alternatives to Relieve Depression) patients with PPS had more severe depressive symptoms and poor treatment outcome correlated also with gender, ethnicity and comorbidi-ty.24 In our sample, patients with ADE and PPS were more ill according to CGI-S. They had more depressive symptoms on HAM--D as well as on Zung Questionnaire and were functionally more disabled as measured with GAS. The same higher depression severity was found in out-patients with major depressive disorder with PPS.11 In contrast to a recent study where suicidality was higher in patients with PPS, the history of suicide attempt was common in all patients reflecting the high suicide risk in Slovenian population.20'25
More than 80 % of the patients in both groups were prescribed serotonin and no-repinephrine reuptake inhibitors (SNRIs), which might reflect the influence of reported efficacy of novel dual acting antidepressants and local effect. One third of the patients received mood stabilizers (antiepileptics) for augmentation of antidepressant efficacy in severe depression, as recommended in therapeutic guidelines. 2® High proportion of analgesic use was found in patients with PPS, which raises the question of rational pharmacotherapy, since these patients had no clear somatic co-morbidity. Most of the patients were treated with paracetamol and NSAIDs. Although not as dangerous as opi-oids, these drugs can still cause dependence, hepatotoxicity, renal failure and cardiovascular complications. 2y Rational therapy for co-morbid depression and PPS based on literature recommendations would be double-acting agents (duloxetine, venlafaxi-ne, mirtazapine, bupropion, nefazodon and triclycic antidepressants) and antiepileptics (carbamazepine, lamotrigine, pregabalin and neurontin). 12-28-30
Conclusions
There is a vast body of literature on pain and depression, with most of the studies conducted in primary care, in other specialties and focusing primarily on pain. The growing interest of properly diagnosing PPS in depression is also influenced by literature reports on the therapeutic efficacy of SNRIs on pain. However, there is still a lack of studies on epidemiology of pain in depression in psychiatric settings, especially in acute and severe episode of depression. The sample in our study was relatively small but pure, excluding patients with a co-morbid somatic illness. The results are partly in concordance with findings in other studies: the high prevalence of PPS, which is associated with more severe symptoms of depression. The results confirm that patients with ADE should be carefully examined and treated for all symptoms, and that the pharma-cotherapy should be rational, not forgetting the potentially harmful over-prescribing of painkillers.
References
1.	Aguera L, Failde I, Cervilla JA, Diaz-Fernandez P, Mico JA. Medically unexplained pain complaints are associated with underlying unrecognized mood disorders in primary care. BMC Fam Pract 2010; 11: 17.
2.	Katona C, Peveler R, Dowrick C, Wessely S, Feinmann C, Gask L, et al. Pain symptoms in depression: definition and clinical significance. Clin Med 2005; 5: 390-5.
3.	Garcia-Cebrian A, Gandhi P, Demyttenaere K, Peveler R. The association of depression and painful physical symptoms-a review of European literature. Eur Psychiatry 2006; 21: 379-88.
4.	Peveler R, Katona C, Wessley S, Dowrick C. Painful symptoms in depression: under-recognized and under-treated? J Br Psychiatry 2006; 188: 202-3.
5.	Dowrick C, Katona C, Peveler R, Lloyd H. Somatic symptoms and depression: diagnostic confusion and clinical neglect. Br J Gen Pract 2005; 55: 829-30.
6.	Robinson MJ, Edwards SE, Iyengor S, Bymaster F, Clark M, Katon W. Depression and pain. Front Bi-osci 2009; 14: 5031-51.
7.	Bair MJ, Robinson RL, Eckert GJ, Stang PE, Crog-hon TN, Kroenke K. Impact of pain on depression treatment response in primary care. Psychosom Med 2004; 66:17-22.
8.	Karp JF, Scott J, Houck P, Reynolds F 3rd, Kupfer DJ, Frank E. Pain predicts longer time to remission during treatment of recurrent depression. J Clin Psychiatry 2006; 66: 17-22.
9.	Karp JF, Weiner D, Seligman K, Butters M, Miller M, Frank E, et al. Body pain and treatment response in late-life depression. Am J Geriatr Psychiatry 2005; 13: 188-94.
10.	Paykel ES, Ramana R, Cooper Z, Hayhurst H, Kerr J, Barocka A. Residual symptoms after partial remission: An important outcome in depression. Psychol Med 1995; 25: 1171-80.
11.	Reeves RR, Cox SK. Similar effect of tramadol and venlafaxine in major depressive disorder. South Med J 2008; 101: 193-5.
12.	Mohr P, Bitter I, Svedska J, Seifritz E, Karamu-stafalioglu O, Koponen H, et al. Management of depression in the presence of pain symptoms. Psychiatr Danub 2010; 22: 4-13.
13.	Jann MW, Slade JH. Antidepressant agents for the treatment of chronic pain and depression. Phar-macotherapy 2007; 27: 1571-87.
14.	Greden JF. Treating depression and pain. J Clin Psychiatry 2009; 70: 16.
15.	Wise TN, Fishbain DA, Holder-Perkins V. Painful physical symptoms in depression: A clinical challenge. Pain Med 2007; 8 suppl12: s75-s82.
16.	Hamilton M. Development of a rating scale for primary depressive illness. Br J Soc Clin Psychol 1967; 6: 278-96.
17.	Guy W: Clinical Global Impressions (CGI) Scale. Modified From: Rush J.: Psychiatric Measures. Washingtorn DC: APA; 2000.
18.	Hall RC. Global assessment of functioning. A modified scale. Psychosomatics 1995; 36:267-75.
19.	Zung A. A self-rating scale. Arch Gen Psychiatry 1965; 12: 63-70.
20.	Bahk WM, Park S, Jon DI, Yoon BH, Min KJ, Hong JP. Relationship between painful physical symptoms and severity of depressive symptomatology and suicidality. Psychiatry Res 2011; 189: 357-61.
21.	Hartman JM, Berger A, Baker K, Bolle J, Handel D, Mannes A, et al. Quality of life and pain in premenopausal women with major depressive disorder: the POWER Study. http://www.hqlo.com/ content/4/1/2, 2006.
22.	Fornaro M, Maremmani I, Canonico PL, Carbo-natto P, Mencacci C, Muscettola G, et al. Prevalence and diagnostic distribution of medically unexplained painful somatic symptoms across 571 major depressed outpatients. Neuropsychiatr Dis Treat 2011; 7: 217-21.
23.	Arnow BA, Hunkeler EM, Blasey CM, Lee J, Constantino MJ, Fireman B et al. Comorbid depression, chronic pain, and disability in primary care. Psychosom Med 2006; 68: 262-8.
24.	Leuchter AF, Husain MM, Cook IA, Trivedi MH, Wisniewski SR, Gilmer WS, et al. Painful physical symptoms and treatment outcome in major depressive disorder: a STAR*D (Sequenced Treatment Alternatives to Relive Depression) report. Psychol Med 2010; 40 (suppl. 2); 239-51.
25.	Kocmur M, Dernovsek MZ . Attitudes towards suicide in Slovenia; a cross-sectional survey. Int J Soc Psychiatry 2003; 49: 8-16.
26.	Bazaire S. Psychotropic drug directory 2012. Warwickshire: Loyd-Reinhold Communications LPP; 2012.
27.	Labianca R, Sarzi-Puttini P, Zuccaro SM, Cheru-bino P, Velluci R, Fornasari D. Adverse effects associated with non-opioid and opioid treatment in patients with chronic pain. Clin Drug Invest 2012; 32 suppl 1: s53-s63.
28.	Marks DM, Shah MJ, Patkar AA, Masand PS, Park G, Pae C. Serotonin-norepinephrine reuptake inhibitors for pain control: premise and promise. Curr Neuropharmacology 2009; 7: 331-6.
29.	Stahl SM. Stahl's Essential Psychopharmacology. 3rd ed. Cambridge: University Press; 2008.
30.	Maj M, Sartorius N, Tasman A, Gureje O. WPA educational programme on depressive disorders. Vol 2, The World Psychiatry Association; 2008.