Major Depression: A Short Term Naturalistic Study in Outpatients

Transcription

1 DELHI PSYCHIATRY JOURNAL Vol. 14 No.1 APRIL 2011 Original Article 70 Major Depression: A Short Term Naturalistic Study in Outpatients Introduction Madhusudan*, Vankar GK**, Brahmbhatt M**, Rastogi R*, Verma P* *Department of Psychiatry Safdarjung Hospital & VMMC **Department of Psychiatry BJMC & Civil Hospital Ahmedabad Major depressive disorder is the most common disabling treatable condition diagnosed in psychiatric and primary care settings. WHO has ranked depression fourth in a list of most urgent health problem worldwide. hence studying its presentation, course, treatment response and outcome becomes important. 1-3 Treatment response and outcome often differs in Naturalistic conditions than controlled trials. Many Naturalistic studies in various parts of the world have explored course and outcome of major depressive disorder, envisaging on one hand studying its early course to subjects followed up years together being treated in natural clinical settings. 4-6 Surprisingly there are no ABSTRACT Background: Surprisingly data regarding naturalistic or observational studies carried out in India to study Major Depressive Disorder in patients seeking outpatient treatment is almost non-existing. So this study was conducted to study the presentation and baseline characteristics of Major Depressive Disorder in Indian outpatients and the subsequent treatment and outcome after a three month follow up. Methodology: Patients seeking outpatient treatment were recruited after diagnosing an episode of Major Depressive Disorder through a clinical interview for DSM IV TR. Sociodemographic and clinical characteristics were recorded at the time of recruitment and follow up evaluations done for 3 months. All the patients were given outpatient treatment best suited to the patient profile. Results :.More than 90% patients reported one or more somatic symptoms spontaneously on presentation. Barely half of the patients out of 119 recruited completed three month follow up. 50 (81%) patients out of 62 who received adequate treatment met recovery criteria at the end of three months. Initial depression severity and receiving regular adequate antidepressant therapy was found to be associated with recovery. While sociodemographic variables were not found to significantly affect treatment outcome or compliance. Conclusion : Somatic presentation of depression is quite common in Indian patients.the high noncompliance indicate the need for strategies to be made to improve compliance and the good response to treatment found in naturalistic conditions in this study calls for more such studies to be done for better understanding of predictors of outcome in naturalistic conditions in India. Key Words: Major depression, naturalistic study, outpatients. published naturalistic studies in India on Major Depressive Disorder up to best of our knowledge. All this prompted us to take up this first of its kind study ever done with Indian depressed Outpatients. This study documents the presentation, early course and outcome of major depressive disorder in psychiatric outpatients treated in naturalistic conditions and sees whether intensive regular antidepressant therapy is associated with recovery. Materials and Methods Study was conducted at psychiatric OPD civil hospital Ahmedabad. Patients presenting with depression for the first time in psychiatric OPD seeking outpatient treatment were recruited. Written

2 APRIL 2011 DELHI PSYCHIATRY JOURNAL Vol. 14 No.1 informed consent was obtained prior to induction of subjects into the study. Patients were diagnosed as having Major depression by a clinical interview by psychiatry residents and consultants based on DSM-IV TR diagnostic criteria. 7 Exclusion criteria were depression secondary to schizophrenia and dementia, presence of psychotic symptoms, actively suicidal patient, comorbid general medical condition directly contributing to depression (eg hypothyroidism), comorbid substance use disorder or presence of bipolar disorder. A total of 119 patients were recruited over a period of 10 months. Baseline sociodemographic and clinical variables of each patient were recorded at the time of presentation. Severity of depression on presentation and subsequent follow ups was assessed using 24 item HDRS scale. 8 Patients were followed up to a period of 3 months with follow up evaluations and assessment of severity and treatment response done at 15 days, one month and at the end of three months. Each patient was given an antidepressant best suited to the patient profile; adequate treatment was defined as drug being given in therapeutic doses (eg. 20 mg fluoxetine, 150 mg Imipramine or equivalent.) with regular follow-ups for a period of three months. The absence of the above two was considered as inadequate treatment. The therapeutic doses were reached in 15 to 20 days. A score of 7 or less than 7 on HDRS was considered as remission. While greater than 50% reduction in initial symptoms score was considered as response. Data was analyzed and statistical tests were applied as appropriate. Two-tailed P values of less than.05 were considered statistically significant. Results 1. Socidemographic characteristics. A total of 119 depressed patients coming for the first time in psychiatric OPD seeking outpatient treatment were recruited. Age of patients ranged from 18 to 65(mean age = years). Around 48% of the patients were males and 52% were females. 87% had urban background while 13% were from rural areas. Almost 3/4th of the patients (76%) were married while 1/4th were single (unmarried, divorced, separated, and widowed). Majority of patients (66%) were employed either in skilled (27%) or unskilled jobs (39%), a good no of patients were housewives (28%) while only a few 7% were unemployed, retired or students. Around 18% of them were illiterate, only 13% had studied up to graduate level while the rest had education up to primary or high school level. Most of them (74%) had monthly income of Rupees 5000 or less. Half of the patients (50%) belonged to joint families. Depression severity at presentation: Clinical variables and symptomatic presentation If we look at the baseline severity then 54 % patients fell into the mild to moderate category, 29% were having severe depression while only 17% had Table-1. Depression Severity at Presentation Patients Mild Mod. depression Severe Very Severe depression HDRS score depression depression HDRS* score HDRS score HDRS score (8-13) (14-18) (19-22) (>23) 24(20)* 41(34) 34(29) 20(17) Patients with regular 3 12 (19) 20 (32) 21 (34) 9 (15) month fup= 62 Patient with irregular 1 (10) 5 (50) 2 (20) 2 (20) fup=10 Patient lost to fup =47 11 (23) 16 (34) 11 (23) 9 (19) * Data are given as number (percentage) of patients in the table. HDRS: Hamilton Depression Rating Scale. 71

3 DELHI PSYCHIATRY JOURNAL Vol. 14 No.1 APRIL 2011 Table-2a. Baseline Clinical Characteristics Descriptor Total no of Patients with Patient with Patient lost Stat. patients 3 month f up irregular f up to f up analysis (N = 119) (n = 62) ( n = 10) ( n= 47) Baseline HDRS (4.70) (4.83) (4.19) (4.73) ANOVA Scores, mean (SD)* p=0.971 Duration 2=.0038 < 6 month 96 (81) 50 (81) 8 (80) 38 (81) df=2p > 6 months 23 (19) 12 (19) 2 (20) 9 (19) =0.998 Past history of 2=1.956 depression 16 (13) 10 (62) 0 6 (13) df=2p Present Absent 103 (87) 52 (84) 10 (100) 41 (87) =0.376 Family history Nil 102 (80) 53 (85) 9 (90) 40 (85) 2=.1669 Positive for 8 (07) 4 (06) 0 4 (09) df=2p depression 3 (06) =0.919 Positive for any 9 (08) 5 (08) 1 (10) other psychiatric illness Psychosocial stressor 2=2.432 Present 76 (64) 36 (58) 6 (60) 34 (72) df=2 Absent 43 (36) 26 (42) 4 (40) 13 (28) p=0.296 *Data are given as mean (SD) in the upper row and given as number (percentage) of patients in the lower rows. HDRS: Hamilton Depression Rating Scale. very severe depression (table1). Majority of patients 63% were having duration of depression between 1 to 6 months, 18% had depressive symptoms for less than one month while 19% had duration greater than 6 months. Very few patients (13%) had past history of a depressive episode while only 7% had family history of depression (table 2a). One or mor e somatic symptoms (most commonly pain, heaviness in head, sleep disturbance, and decreased appetite) were at first spontaneously reported by 91 % of the patients when they presented while further inquiry revealed cognitive and emotional symptoms characteristic of depression. Among the depressive symptoms, sad mood (100%), lack of interest (98%), sleep disturbance (90%), and fatigue (90%) were the most commonly encountered symptoms (table2b). There was not found any significant difference between baseline Sociodemographic and Clinical variables of subjects with regular follow ups, irregular follow ups or those who were lost to follow up. Drop out rate was quite high and only 62 patients Table-2b. Symptom Presentation Symptoms % of patients Sad mood 100 Lack of interest 98 Sleep disturbance 90 Fatigue /LOE 90 Wt loss/red app 86 Worth/helpless 80 Forgetfulness 45 PMA/retardation 38 Death wishes 34 (52%) completed regular three month follow up, 10 patients ( 8%) came for irregular follow ups while 47 patients (39%) were lost to follow up. Presence or absence of psychosocial stressor was not found to be significantly associated with compliance. ( 2=2.432, df=2, p=0.296). Treatment given Majority of patients (74%) received an SSRI, 72

4 APRIL 2011 DELHI PSYCHIATRY JOURNAL Vol. 14 No.1 20% received a Tricyclic Antidepressant while only 4 patients were given both in succession, out of these 2 patients were shifted from a TCA to SSRI due to not tolerating the side effects of TCAs. There was not found any significant association between class of drug given and treatment compliance and response ( 2 =.899 df =2 p =.63). Comparison of recovered and non-recovered subjects. Out of the 62 patients completing regular three months follow up 50 subjects (81%) met recovery criteria, compared to only 2 subjects (20%) with irregular follow up and inadequate treatment. Thus remission was found to be significantly associated with intensive adequate pharmacotherapy. ( 2 =12.9, df=1, p=0.0001) Table-3a. Treatment response and outcome at the end of three months. Rx Regular Irregular response N=62 (%) N=10 (%) Remitted 50 (81) 2 (20) Partial recovery 7 (11) 0 (0) Non responders 5 (8) 8 (80) ( 2 =12.9, df=1, p=0.0001) In the 62 regular follow up patients, 7 patients (11%) did not meet recovery criteria but they met the criteria for response. 5 patients (8%) did not even show response at the end of three months assessment. Out of the 10 patients completing three-month irregular follow up with inadequate treatment only 2 patients (20%) met recovery criteria while 8 patients (80%) were still having significant depressive symptoms at the end of three months. On comparing the recovered and non-recovered subjects clinical variable of lower baseline HDRS scores was found to be significantly associated with recovery. (t = df = 61, p<0.0001). None of the sociodemographic variables was found to be associated with recovery or treatment response in patients who recovered or who did not recover. Similarly presence or absence of psychosocial stressor was not found to be significantly associated with recovery (p= 0.745) (table3b). Discussion Looking at the presentation we interestingly found that most patients with depression at first spontaneously reported one or more somatic symptoms (mostly pain, heaviness in head, sleep disturbance, decreased appetite) while typical depressive symptoms were revealed on further probing. This finding is in accordance with similar finding in Indian depressed patients reported previously by Weiss et al. 9 Somatic symptoms of vague aches and pains are extremely common in depression. In non-western cultures, most patients with depression present with somatic complaints. Many non-western cultures use somatic idioms for low mood and sadness, but detailed inquiry usually reveals cognitive and emotional symptoms typical of depression. 10 Although there is now growing evidence that somatic symptoms are common presenting features of depression throughout the world The reason for this somatic presentation of depression may be as it has been suggested previously that somatization is a concept that reflects the dualism inherent in Western biomedical practice, whereas in most of the great traditions of medicine (such as Chinese or ayurvedic medicine) a sharp distinction between the mental and the physical does not occur. 15 Similarly it has been said that people from traditional cultures may not distinguish between the emotions of anxiety, irritability and depression because they tend to express distress in somatic terms. 16 Compliance is a major problem in depression as in our study too 40% patients were lost to follow up while 8% came for irregular follow ups, this finding is in accordance with previous studies which have reported drop out rates of 30 to 60% in depressed out patients. 17,18 Similar findings have been reported previously by Lin et al. 19 that contrary to clinical practice guidelines for the treatment of depression, which recommend at least 6 to 9 months of continuous therapy, they found that 28% of patients discontinue antidepressant treatment within the first month of therapy, and more than 40% of patients discontinue this therapy by 3 months. In this study there was not found any significant association between class of drug (either SSRI or TCAs) given and treatment compliance and response as has been found previously by Song et al (1993). 20 There was not found any significant difference 73

5 DELHI PSYCHIATRY JOURNAL Vol. 14 No.1 APRIL 2011 Table-3b. Baseline clinical characteristics of recovered and non recovered subjects Descriptor Total no of Recovered Non t test df p value patients with patients recovered regular 3 patients month follow up(n=62) (n=50) (n=12) 24 item HDRS score 18.19(4.83) 17.74(4.90) 20.08(4.16) < mean (SD)* 2 df p value Duration <6 months 47 (76) 40 (80) 7 (58) >6 months 15 (24) 10 (20) 5 (42) Past history of depression Present 10 (16) 7 (14) 3 (25) Absent 52 (84) 43 (86) 9 (75) Family history Nil 55 (89) 44 (88) 11 (92) Fisher s p= 1.00 Positive for 4 (06) 3 (06) 1 (08) exact depression Positive for 3 (05) 3 (06) 0 any other psychiatric illness Psychosocial stressor Present 36 (58) 28 (56) 8 (67) Fisher s p= Absent 26 (42) 22 (44) 4 (33) exact, *Data are given as mean (SD) in the upper row and given as number (percentage) of patients in the lower rows. HDRS: Hamilton Depression Rating Scale between baseline Sociodemographic and Clinical variables of subjects with regular follow ups, irregular follow ups or those who were lost to follow 6, 21,22 up as has been reported previously also. Comparing the recovered and non-recovered patients we found that none of the sociodemographic variables including marital status or gender was found to be associated with recovery or treatment response in patients who recovered or who did not recover as has been found earlier also while some studies have found better recovery in females and married. 6,21,23-26, The finding in our study that presence or absence of psychosocial stressors was not found to be significantly associated with either recovery or compliance is in congruence with previous studies that have found that clinical variables are more significantly associated with outcome rather than psychosocial stressors but which stands in contrast to other studies that report recovery being affected negatively by the presence of psychosocial stressors 24,25, 34 In our study barely half of the patients were able to achieve the criteria for regular adequate pharmacotherapy and 81 % of them achieved the recovery criteria at the end of three months while various previous studies have found recovery in the range of 33% to 67% with 74

6 APRIL 2011 DELHI PSYCHIATRY JOURNAL Vol. 14 No.1 adequate pharmacotherapy The higher rates of recovery found in our study may be due to: 1. As the outcome was assessed up to three month only, it has been reported earlier also that rate of recovery is highest in first three month after start of treatment than later on. 31,32 2. Data should be interpreted in terms of the definition of recovery used. If the recovery criteria change the results could have been different. 33,34 3. Possible better coping of people belonging to lower socioeconomic class in India, though there is no published study in India to support this hypothesis but in a survey done in 1995 Blue et al. found that Indian women living in slums fared far better in mental health than the same population in Brazil and Chile. 35 A study done in severely depressed patients by Croughan et al (1988) found rate of recovery to be higher in those belonging to lower income group. 36 One finding that came out in our study is that subjects who had lower baseline HDRS scores recovered better than those who had higher baseline HDRS scores i.e. lower baseline HDRS scores are associated with recovery in naturalistic conditions corroborates similar finding previously by Barnett et al (2002). 6 Our study finds that regular intensive antidepressant therapy is associated with recovery in naturalistic conditions which is also in congruence with similar findings previously. 6 The finding that majority of patients seeking out regular treatment for major depression recovered within 3 months speaks to the need for regular adequate treatment. Limitation Majority of the patients belonged to lower socioeconomic strata and hence findings cannot be generalized unless similar studies are carried out involving patients from all sociocultural backgrounds. Conclusion The study finds and strengthens the earlier findings that depressed patients often present with somatic symptoms in India and hence diagnosing depression keeping this fact in mind will probably help clinicians in diagnosing depression correctly in Indian patients. Greater recovery with adequate treatment in clinical settings clearly indicates the importance of regular adequate pharmacotherapy. Looking at the high rate of noncompliance there is a need to make strategies to increase compliance. As the results found in the study are somewhat different from what efficacy trials of drugs and naturalistic studies have reported in the West, it calls for better understanding of predictors of outcome in naturalistic conditions in India. References 1. Kessler RC, Berglund P, Demler O. The Epidemiology of Major Depressive Disorder: Results From the National Comorbidity Survey Replication (NCS-R); JAMA 2003; 289 : Lehtinen V, Joukamaa M. Epidemiology of depression: prevalence, risk factors and treatment situation, Acta Psychiatr Scand, Suppl. 1994; 377: Murray CJ, Lopez AD. Alternative projections of mortality and disability by cause : Global Burden of Disease Study. Lancet 1997; 349: Doi: /S (96) Elkin I, Shea MT, Watkins JT, Imber SD, Sotsky SM, Collins JF, Glass DR, Pilkonis PA, Leber WR, Docherty JP, Fiester SJ, Parloff MB. National Institute of Mental Health Treatment of Depression Collaborative Research Program: general effectiveness of treatments. Arch Gen Psychiatry 1989; 46 : Malt UF, Robak OH, Madsu H-P, Bakke O, Loeb M. The Norwegian naturalistic treatment study of depression in general practice (NORDEP)-I: randomised double blind study. BMJ 1999; 318 : Barnett et al. Predictors of Early Recovery From Major Depression Among Persons Admitted to Community-Based Clinics; Arch Gen Psychiatry 2002; 59 : American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition TEXT REVISION. Washington, DC: American Psychiatric Association; Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960; 23 : Weiss MG, Raguram R, Channabasavanna SM. 75

7 DELHI PSYCHIATRY JOURNAL Vol. 14 No.1 APRIL 2011 Cultural dimensions of psychiatric diagnosis. A comparison of DSM III R and illness explanatory models in south India. Br J Psychiatry 1995; 166 : Bhugra D, Ranjith G, Patel V, Affective Disorders in Handbook of Psychiatry: A South Asian Perspective 2005; (235). 11. Simon GE, Von Korff M, Piccinelli M. An international study of the relation between somatic symptoms and depression. New Engl J Med 1999; 341 : Bhatt A, Tomenson B, Benjamin S. Transcultural patterns of somatisation in primary care: a preliminary report. J Psychosom Res 1989; 33 : Ebert D, Martus P. Somatisation as a core symptom of melancholic type depression: evidence from a cross-cultural study. J Affect Disord 1994; 32 : Katon W, Walker EA. Medically unex-plained symptoms in primary care. J Clin Psychiatry 1998; 59 (suppl. 20) : Kirmayer LJ, Young A. Culture and somatization: clinical, epidemiological and ethnographic perspectives. Psychosom Med 1998; 60 : Leff JP. International variations in the diagnosis of psychiatric illness. Br J Psychiatry 1977; 131 : Demyttenaere K, Haddad P. Compliance with antidepressant therapy and antidepressant discontinuation symptoms, Acta Psychiatr Scand 2000; 101(S403) : Simon G, VonKorff M, Wagner EH, Barlow W. Patterns of antidepressant use in community practice. Gen Hosp Psychiatry 1993; 15: Lin EHB, VonKorff M, Katon W, Bush T, Simon GE, Walker E, Robinson P: The role of the primary care physician in patients adherence to antidepressant therapy. Med Care 1995; 33 : Song F, Freemantle N, Sheldon TA. Selective serotonin reuptake inhibitors compared with tricyclic antidepressants: a meta-analysis of efficacy and acceptability. BMJ, 1993 ; 306 : Perlis RH, Alpert J, Nierenberg AA. Clinical and sociodemographic predictors of response to augmentation, or dose increase among depressed outpatients resistant to fluoxetine 20 mg/day, Acta Psychiatr Scand, 2007; 108 : Bull SA, Hu XH, Hunkeler EM, Lee JY, Ming EE, Markson LE, Fireman B: Discontinuation of use and switching of antidepressants: influence of patient-physician communication. JAMA 2002; 288 : Psychosocial Predictors of Outcome in Depression: Robert M. A. Hirschfeld; Psychopharmacology: The Fourth Generation of Progress, GN /Default.htm. 24. Sergeant JK, Bruce ML, Florio LP, Weissman M. Factors associated with 1-year outcome of major depression in the community. Arch Gen Psychiatry 1990; 47 : Goodyer, Herbert, Joe Tamplin, Alison: Short- Term Outcome of Major Depression: II. Life Events, Family Dysfunction, and Friendship Difficulties as Predictors of Persistent Disorder. J Am Acad Child Adolesc Psychiatry 1997; 36 (4) : Spillmann M, Borus JS, Davidson KG, Worthington JJ III, Tedlow JR, Fava M. Sociodemographic predictors of response to antidepressant treatment. Int J Psychiatry Med 1997; 27 : RM Hirschfeld, GL Klerman, NC Andreasen : Psychosocial predictors of chronicity in depressed patients; Br J Psychiatry 1986; 148 : Thase ME, Entsuah AR, Rudolph RL. Remission rates during treatment with venlafaxine or selective serotonin reuptake inhibitors. Br J Psychiatry 2001; 178 : Casacalenda N, Perry JC, Looper K. Remission in major depressive disorder: a comparison of pharmacotherapy, psychotherapy, and control conditions. Am J Psychiatry 2002 ; 159 : Cuffel BJ, Azocar F, Tomlin M, Greenfield SF, Busch AB, Croghan TW. Remission, residual symptoms, and nonresponse in the usual treatment of major depression in managed clinical practice. J Clin Psychiatry 2003; 64 :

8 APRIL 2011 DELHI PSYCHIATRY JOURNAL Vol. 14 No Keller MB, Klerman GL, Lavori PW, Coryell W, Endicott J, Taylor J. Long-term outcome of episodes of major depression: clinical and public health significance. JAMA 1984; 252 : Keller MB, Shapiro RW, Lavori PW, Wolfe N. Recovery in major depressive disorder: analysis with the life table and regression models. Arch Gen Psychiatry 1982; 39 : Frank E, Prien RF, Jarrett RB, Keller MB, Kupfer DJ, Lavori PW, Rush AJ, Weissman MM: Conceptualization and rationale for consensus definitions of terms in major depressive disorder. Arch Gen Psychiatry 1991; 48 : Zimmerman M, Posternak MA, Chelminski I. Implications of using different cut-offs on symptom severity scales to define remission from depression. Int Clin Psychopharmacol 2004; 19 : Blue I, Ducci ME, Jaswal S. The mental health of low income urban women. In Urbanisation and Mental Health in Developing Countries (edst. Harpham and I. Blue), Aldershot: Avebury 1995; pp Croughan JL, Secunda SK, Katz MM. Sociodemographic and prior clinical course characteristics associated with treatment response in depressed patients. J Psychiatr Res 1988; 22 (3) :