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Psychosocial functioning in patients with treatment resistant depression
European Psychiatry 19 (2004) 196–201 www.elsevier.com/locate/eurpsy
Original article
Psychosocial functioning in patients with treatment resistant depression Timothy Petersen *, George I. Papakostas, Yasmin Mahal, Wendy M. Guyker, Erin C. Beaumont, Jonathan E. Alpert, Maurizio Fava, Andrew A. Nierenberg Department of Psychiatry, Depression Clinical and Research Program, Massachusetts General Hospital, 15 Parkman Street, WAC 812 Boston, MA 02114, USA Received 15 March 2003; received in revised form 24 October 2003; accepted 20 November 2003 Available online 25 May 2004
Abstract Background. – Depression is a disorder that causes disability, with a profound adverse impact on all areas of psychosocial functioning. This is particularly true for those with treatment resistant depression (TRD). However, to date, no systematic assessments of psychosocial functioning for patients with TRD have been conducted. Methods. – In the present study, we used the Longitudinal Interval Follow-up Evaluation (LIFE) scale to measure psychosocial functioning in 92 patients with TRD. These patients met formal criteria for TRD and were part of a clinical trial examining the efficacy of lithium augmentation of nortriptyline. Results. – Clinicians rated this sample of patients as experiencing mild to moderate impairment in work-related activities, good to fair interpersonal relations, poor level of involvement in recreational activities, and mild impairment of ability to enjoy sexual activity. Patients and clinicians rated global social adjustment as poor. Conclusions. – Patients with formally defined TRD experience significant impairment in psychosocial functioning. In this sample a tendency existed for both clinicians and patients to assign more severely impaired global ratings when compared with ratings for specific functional areas. © 2004 Published by Elsevier SAS. Keywords: Treatment resistant depression; Psychosocial functioning
1. Introduction Depression is an illness associated with significant chronicity and disability and has a profound impact on psychosocial functioning [29]. Unipolar depression is currently the leading cause of disability in developed countries [43], and the fourth leading cause of disability worldwide [25]. Projections estimate that depression will rise to be the second leading cause of worldwide disability by the year 2020 [24]. Depression has also been shown to account for a 23-fold increase in social disability even after controlling for physical disease [27], as well as a 3.2 to 5-fold increase in shortterm work-disability days [3,19,28]. In fact, the impact of depression on wellbeing is comparable to or greater than many chronic medical conditions [42]. Overall, the annual cost of depression to society is estimated to be 44 billion dollars [10], 12 billion of which is accounted for by disability * Corresponding author. E-mail address: [email protected] (T. Petersen). © 2004 Published by Elsevier SAS. doi:10.1016/j.eurpsy.2003.11.006
[22]. These estimates do not include the added cost of treating medical conditions in depressed patients compared to their non-depressed counterparts [37]. In view of the debilitating impact of depression on psychosocial functioning and the expected increase in disability worldwide, research is urgently needed to further assess the spectrum of dysfunction in major depressive disorder (MDD). We believe this is particularly true for those with treatment resistant depression (TRD), a severely ill segment of the depressed population in terms of chronicity, comorbidity, prognosis and outcome [21]. From an epidemiological perspective, assuming the lifetime prevalence of MDD to be approximately 5%, and a non-response rate of 15%, nearly 2 million Americans could suffer from treatment resistant depression at some point in their lives [30]. It appears that 29–46% of depressed patients show only partial or no response to antidepressants [7]. In fact, 21% of patients who seek treatment for depression fail to recover in up to 2 years, and 12% of patients fail to recover after 5 years [6,16,18]. Furthermore, TRD episodes represent 50% of the annual
T. Petersen et al. / European Psychiatry 19 (2004) 196–201
costs associated with the treatment of depression [33]. Despite these figures, no separate disability assessments have been compiled for treatment resistant depression [9]. The ability to objectively measure psychosocial functioning in clinical trials of TRD is important since a number of studies suggest that psychosocial dysfunction in patients with MDD contributes to antidepressant resistance. Marital disputes were found to predict non-response after 8 weeks of amitriptyline treatment in 76 depressed patients [32], while adequacy of personal and social resources were found to predict response to a 4-week trial of amitriptyline [5]. A study of 116 patients with melancholic depression treated with phenelzine or imipramine identified social support as a predictor of response after 6 weeks and 6 months of treatment [40]. In addition, a 12 week-double blind trial of sertraline vs. imipramine of 600 patients suffering from chronic depression revealed that higher education, living with a partner and higher baseline quality of life predicted positive outcome [12]. A good employment history was found to predict lower post-treatment depressive symptoms in a study of 218 women that were randomized to receive some combination of group psychotherapy, imipramine or individual therapy [4]. In a recent study by Pyne et al. [31], the quality of wellbeing [13] subscales for physical and social activity predicted treatment response with 86% accuracy in depressed inpatients. Studies in MDD also show psychosocial impairment to confer a poor long-term course. Long-term studies of depressed patients identify better family functioning [14], higher life satisfaction scores [20], lower family conflict and adequate family support as predictors of good outcome after 1 year of treatment [23]. Conversely, marriage, a small social network and impaired social support were found to predict poor treatment outcome after 32 months of treatment [8]. Akiskal [1] reports multiple losses as a risk factor for the development of chronic MDD, defined as depression of two or more years duration. In men, unemployment was identified as a risk factor for the development of chronic depression [36], while in both men and women, dissatisfaction with work at baseline was strongly associated with an increased risk of depression 12–25 years in the future [34]. Similarly, unemployed men and women on welfare at baseline were found to have higher MDD indices after 5 years compared to employed men and women [35]. The purpose of this study was to assess the spectrum of psychosocial dysfunction in a group of outpatients with treatment resistant depression. We hypothesized that this sample of patients would be experiencing low levels of psychosocial functioning across multiple domains. 2. Subjects and methods 2.1. Patient selection and study design Subjects were recruited at the Depression Clinical and Research Program (DCRP) of Massachusetts General Hospi-
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tal (MGH) for the purposes of a 6-week, double-blind, placebo-controlled trial to assess the efficacy of lithium (Li) augmentation of nortriptyline (NT) for subjects with TRD who had previously failed a 6-week open trial of NT. The data presented in this paper were collected during the screening visit for the open phase of the study. Subjects were recruited through clinical referrals and advertisement. In the latter case, prospective participants responded to newspaper and radio advertisements. These advertisements listed common symptoms of depression and instructed respondents to leave a message at a central phone number if they believed they were experiencing any of these symptoms. Prospective participants who had been referred by other clinicians or had responded to the advertisement were scheduled for a screen visit. The screen visits were conducted by one of the staff psychiatrists or psychologists at the Massachusetts General Hospital Depression Clinical and Research Program (DCRP), all of whom were trained in the use of all scales involved in this study. During the screen visit a structured clinical interview was conducted and a formal determination was made as to the patient’s eligibility for the study. A total of 92 outpatients were enrolled. Inclusion criteria were as follows: men and women ages 18–70 with major depressive disorder (MDD) diagnosed using the Structured Clinical Interview for the DSM-III-R—Patient Edition [39], and a score on the 17-item Hamilton Depression Rating Scale [11] greater than or equal to 18. Treatment resistance was defined as at least one, but no more than five adequate failed trials during the current depressive episode. An adequate trial was defined with the use of the Harvard Antidepressant Treatment History Form [26], which provides specific criteria for the dose and length of a trial to be considered adequate. Exclusion criteria for this trial were defined as follows: bipolar I or II disorder, psychosis, a history of organic mental or seizure disorder, serious or unstable medical illness, substance abuse disorders active within the past 12 months, acute suicidal risk (as assessed through clinical interview and using the HAM-D-17), pregnancy, lactation, history of adverse reaction or allergy to the study medications, concomitant use of psychotropic medications, and clinical or laboratory evidence of thyroid abnormalities. Participants in this study signed an Institutional Review Board (IRB) approved informed consent during the screen visit. 2.2. Measurement of psychosocial functioning Several scales have been developed to measure psychosocial functioning [41]. The Longitudinal Interval Follow-up Evaluation (LIFE) scale was developed during the National Institute for Mental Health (NIMH) collaborative study of the psychobiology of depression [15]. It provides an organized and comprehensive method to record the retrospective and prospective course of illness and treatment. The advantages of the LIFE scale are that it is established and reliable, especially for retrospective assessment of treatment history [17].
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In the present study, the LIFE sub-scale for psychosocial functioning was administered during the screen visit. This clinician-administered sub-scale contains a section designed to measure psychosocial functioning in five specific domains—work, interpersonal relations, sexual functioning, overall satisfaction and recreation. The first three of these domains contain sub-domains as follows: Domain Work Interpersonal relations Sexual functioning
Sub-domains Employment, household duties, student wo rk Spouse, children, other relatives, friends Enjoyment, frequency
In addition, our study focused on three additional items. Two of these represent a patient and a clinician rated item focusing on the global assessment of social adjustment. The last item represents a clinician rating of the reliability of the information gathered for the LIFE assessment. Each of the five LIFE domains and two global assessment items are scored on a five point scale, with (1) representing a high level of functioning (very good), (2) satisfactory functioning (good), (3) mild impairment (fair functioning), (4) moderate impairment (poor functioning), and (5) severe impairment (very poor functioning). For each domain and item, two scores are assigned—one reflecting function during the past month and a second score reflecting best functioning during the past 5 years. For the item reflecting the rater’s assessment of reliability and completeness of the information gathered, a five point scale is used as follows: 1, very good, 2, good, 3, only fair, 4, poor, and 5, very poor. For the current study, we examined the LIFE domain and item scores obtained during the screen visit that reflect function both during the past month, and best functioning during the past 5 years.
Table 1 Longitudinal Internal Follow-up Evaluation (LIFE) scale scores Work Employment Hours/week last month Hours/week last 5 years Impairment last month Impairment last 5 years Household duties Impairment last month Impairment last 5 years Student work Impairment last month Impairment last 5 years
19.1 27.6 3.2 1.8 3.1 1.8 3.6 2.4
Interpersonal relations Spouse last month Spouse last 5 years Children last month Children last 5 years Relatives last month Relatives last 5 years Friends last month Friends last 5 years
2.6 2.1 2.2 1.7 3 2.7 3.1 2.1
Sexual functioning Enjoyment last month Enjoyment last 5 years Frequency last month Frequency last 5 years
2.7 2.5 4 2.7
Overall satisfaction Satisfaction last month Satisfaction last 5 years
4.2 2.7
Recreation Recreation last month Recreation last 5 years
4 2.3
Descriptive analyses for continuous and nominal variables were used to characterize the LIFE subscale for psychosocial functioning scores in this sample.
Patient global assessment of social adjustment Last month Last 5 years
4.5 2.9
3. Results
Clinician global assessment of social adjustment Last month Last 5 years
4.4 2.7
Overall social adjustment
1.4
2.3. Statistical analysis
The mean age of our sample (n = 92) was 41.1 ± 11.7 years; 90% were Caucasian; 50% were female; 73% were single; 52% were employed; and 47% were college educated. The mean age of onset of depression was 22.4 ± 14.1 years, the mean duration of the current depressive episode was 96.2 ± 114.4 months and the mean baseline HAM-D-17 score was 21.3 ± 3.9. The mean NT dose and blood levels at week 6 of the open trial were 121.2 ± 33.7 mg and 101.0 ± 50.5 ng/ml, respectively. For all patients, the mean number of failed trials during the current major depressive episode was 2.3 ± 1.5. Table 1 presents the LIFE domain/item scores for the entire sample. Of note are the following findings. When rating patient functioning during the last month, clinicians
Rating scale: 1, very good functioning; 2, good functioning; 3, mild impairment; 4, moderate impairment; 5, severe impairment.
report mild to moderate impairment in work related activities (formal employment, household duties, and student work), good to fair interpersonal relations (spouse, children, relatives, and friends), a poor level of involvement in recreational activities and mild impairment of ability to enjoy sexual activity. In contrast to these findings, patient and clinician global assessment of social adjustment were assigned moderate/marked impairment and poor to very poor ratings. In addition, clinicians report of patient global satisfaction (contentment and gratification) received a poor to very poor
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rating. Reliability of information gathered was assigned a very good to good rating. When comparing functioning during the last month with best functioning during the last 5 years, it is clear that current functioning was rated as significantly worse. The range of difference in functioning between these two time frames was 0.2–1.7 (points on the LIFE scale).
4. Discussion To our knowledge, this is the first study to report on measures of psychosocial functioning in a sample of depressed patients formally defined as treatment resistant. Results indicate that clinicians rated patients’ functioning during the last month as mild to moderately impaired in several specific areas (work activities, interpersonal relations, and sexual relations) and as moderately to severely impaired in recreational activities. When examining global ratings of functioning, raters and patients evidenced a tendency to assign lower ratings of functioning (moderate/marked impairment or poor/very poor). In addition we found a significant contrast between ratings of current functioning and ratings of best functioning within the last 5 years, with the former receiving lower ratings. The discrepancy between specific and global ratings of functioning could be accounted for by a tendency for patients to assign lower ratings when a global question is posed. We are not aware of any previous studies that have evaluated this phenomenon. However, previous research does suggest that, when in the midst of a depressive episode, patients have the tendency to make negative, global attributions [2]. In addition, a key concept in the conceptualization of depression by cognitive therapists is distorted thinking. Cognitive distortions that relate to this tendency of assigning negative global ratings are “all or none thinking” and catastrophizing. Clinical experience also suggests that patients readily assign very global descriptions to their functioning (i.e. clinician asks “how have you been feeling?” and the patient responds “terribly”), but when pressed to describe functioning in specific domains a more mixed pattern is observed. Thus, the cognitive style associated with depression (that has been empirically validated) could directly contribute to the phenomenon we describe above. Clinicians, during the screening visit for this protocol, gathered very detailed information about chronic symptoms and past ineffective treatments. It is possible that a global picture of patient distress emerged during this process that influenced assignment of global ratings of psychosocial functioning. The primary strengths of this study were the use of structured interview instruments including the SCID-P, HAM-D17, and LIFE scale, and formal definition of treatment resistance (using the HATH). The latter resulted in a patient sample with well-characterized treatment resistant unipolar depression. One limitation of this study is the effect of depressive state on patients’ report of psychosocial functioning.
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During the midst of a major depressive episode patients may evidence the tendency to over report functional impairment, although in this case global ratings were probably affected in this way more than specific ratings. Another limitation of the study is that the LIFE scale does not provide a convention for higher order scale scores in the psychosocial domains measured; rather, we report LIFE psychosocial functioning subscale scores. Our method, however, is consistent with both a recent, prominent article [38] in which these scores are reported in the same manner and an article written by the original author of the LIFE scale [15] where no other convention is suggested. Also, we do not report standard deviations for any mean scores of the five-point Likert scale. With respect to ceiling and/or floor effects, few mean scores for our sample’s LIFE psychosocial functioning scales are at either extreme of the five-point Likert scale. Thus, we do not feel a ceiling or floor effect is of any significance. An additional limitation of the study is the exclusion criteria used. Because of these criteria, this sample may not represent treatment resistant patients in general, and in turn, typical levels of psychosocial functioning found in this population. It is reasonable to believe that significantly more psychiatric or medical comorbidity could lower levels of functioning considerably, and have changed our results. As a final note, the average duration of the current major depressive episode for this sample was unusually long –96.2 ± 114.4 months. Because of this, it is possible that level of functioning was not reflective of an acute depressive episode, but rather of a chronic episode. Perhaps more acute impairment was evidenced at the onset of the episode and then moderated after such a lengthy period of time. Patients with such protracted episodes may learn coping skills that allow them to function better in the areas that are measured by the LIFE subscale of psychosocial functioning. The results of this study suggest the need for more careful assessment of psychosocial functioning within the treatmentresistant depressed patient population. Assessment of such functioning can clearly guide treatment efforts. As an example, after careful assessment with an instrument such as the LIFE, a psychotherapist could more easily identify, with the patient, specific target areas to focus on in treatment. In addition, such an assessment process could allow a psychopharmacologist to select medications that would target symptoms associated with the particular problem area (e.g. irritability associated with marital conflict). Finally, proper assessment of psychosocial functioning and appropriate treatment modifications is in line with a recent emphasis in the literature regarding achieving full remission from the disorder rather than simply response. Available evidence suggests that achieving full remission confers a better longterm prognosis for patients who have suffered with depression. Future research is needed to elucidate the impact of treatment resistance on psychosocial functioning. Results of the ongoing NIMH-funded Sequenced Treatment Alternatives to Relieve Depression (STARD) trial will prove helpful in this regard.
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5. Conclusion To our knowledge, this is the first study to assess psychosocial functioning in a sample of patients formally defined as treatment resistant. Results suggest that clinicians rated patients’ functioning during the last month as mild to moderately impaired in several specific areas (work activities, interpersonal relations, and sexual relations) and as moderately to severely impaired in recreational activities. When examining global ratings of functioning, raters and patients evidenced a tendency to assign lower ratings of functioning (moderate/ marked impairment or poor/very poor). Future research is needed to elucidate the impact of treatment resistance on psychosocial functioning.
Acknowledgements Supported in part by NIMH grant R29 MH46952 (AAN).
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Original article
Psychosocial functioning in patients with treatment resistant depression Timothy Petersen *, George I. Papakostas, Yasmin Mahal, Wendy M. Guyker, Erin C. Beaumont, Jonathan E. Alpert, Maurizio Fava, Andrew A. Nierenberg Department of Psychiatry, Depression Clinical and Research Program, Massachusetts General Hospital, 15 Parkman Street, WAC 812 Boston, MA 02114, USA Received 15 March 2003; received in revised form 24 October 2003; accepted 20 November 2003 Available online 25 May 2004
Abstract Background. – Depression is a disorder that causes disability, with a profound adverse impact on all areas of psychosocial functioning. This is particularly true for those with treatment resistant depression (TRD). However, to date, no systematic assessments of psychosocial functioning for patients with TRD have been conducted. Methods. – In the present study, we used the Longitudinal Interval Follow-up Evaluation (LIFE) scale to measure psychosocial functioning in 92 patients with TRD. These patients met formal criteria for TRD and were part of a clinical trial examining the efficacy of lithium augmentation of nortriptyline. Results. – Clinicians rated this sample of patients as experiencing mild to moderate impairment in work-related activities, good to fair interpersonal relations, poor level of involvement in recreational activities, and mild impairment of ability to enjoy sexual activity. Patients and clinicians rated global social adjustment as poor. Conclusions. – Patients with formally defined TRD experience significant impairment in psychosocial functioning. In this sample a tendency existed for both clinicians and patients to assign more severely impaired global ratings when compared with ratings for specific functional areas. © 2004 Published by Elsevier SAS. Keywords: Treatment resistant depression; Psychosocial functioning
1. Introduction Depression is an illness associated with significant chronicity and disability and has a profound impact on psychosocial functioning [29]. Unipolar depression is currently the leading cause of disability in developed countries [43], and the fourth leading cause of disability worldwide [25]. Projections estimate that depression will rise to be the second leading cause of worldwide disability by the year 2020 [24]. Depression has also been shown to account for a 23-fold increase in social disability even after controlling for physical disease [27], as well as a 3.2 to 5-fold increase in shortterm work-disability days [3,19,28]. In fact, the impact of depression on wellbeing is comparable to or greater than many chronic medical conditions [42]. Overall, the annual cost of depression to society is estimated to be 44 billion dollars [10], 12 billion of which is accounted for by disability * Corresponding author. E-mail address: [email protected] (T. Petersen). © 2004 Published by Elsevier SAS. doi:10.1016/j.eurpsy.2003.11.006
[22]. These estimates do not include the added cost of treating medical conditions in depressed patients compared to their non-depressed counterparts [37]. In view of the debilitating impact of depression on psychosocial functioning and the expected increase in disability worldwide, research is urgently needed to further assess the spectrum of dysfunction in major depressive disorder (MDD). We believe this is particularly true for those with treatment resistant depression (TRD), a severely ill segment of the depressed population in terms of chronicity, comorbidity, prognosis and outcome [21]. From an epidemiological perspective, assuming the lifetime prevalence of MDD to be approximately 5%, and a non-response rate of 15%, nearly 2 million Americans could suffer from treatment resistant depression at some point in their lives [30]. It appears that 29–46% of depressed patients show only partial or no response to antidepressants [7]. In fact, 21% of patients who seek treatment for depression fail to recover in up to 2 years, and 12% of patients fail to recover after 5 years [6,16,18]. Furthermore, TRD episodes represent 50% of the annual
T. Petersen et al. / European Psychiatry 19 (2004) 196–201
costs associated with the treatment of depression [33]. Despite these figures, no separate disability assessments have been compiled for treatment resistant depression [9]. The ability to objectively measure psychosocial functioning in clinical trials of TRD is important since a number of studies suggest that psychosocial dysfunction in patients with MDD contributes to antidepressant resistance. Marital disputes were found to predict non-response after 8 weeks of amitriptyline treatment in 76 depressed patients [32], while adequacy of personal and social resources were found to predict response to a 4-week trial of amitriptyline [5]. A study of 116 patients with melancholic depression treated with phenelzine or imipramine identified social support as a predictor of response after 6 weeks and 6 months of treatment [40]. In addition, a 12 week-double blind trial of sertraline vs. imipramine of 600 patients suffering from chronic depression revealed that higher education, living with a partner and higher baseline quality of life predicted positive outcome [12]. A good employment history was found to predict lower post-treatment depressive symptoms in a study of 218 women that were randomized to receive some combination of group psychotherapy, imipramine or individual therapy [4]. In a recent study by Pyne et al. [31], the quality of wellbeing [13] subscales for physical and social activity predicted treatment response with 86% accuracy in depressed inpatients. Studies in MDD also show psychosocial impairment to confer a poor long-term course. Long-term studies of depressed patients identify better family functioning [14], higher life satisfaction scores [20], lower family conflict and adequate family support as predictors of good outcome after 1 year of treatment [23]. Conversely, marriage, a small social network and impaired social support were found to predict poor treatment outcome after 32 months of treatment [8]. Akiskal [1] reports multiple losses as a risk factor for the development of chronic MDD, defined as depression of two or more years duration. In men, unemployment was identified as a risk factor for the development of chronic depression [36], while in both men and women, dissatisfaction with work at baseline was strongly associated with an increased risk of depression 12–25 years in the future [34]. Similarly, unemployed men and women on welfare at baseline were found to have higher MDD indices after 5 years compared to employed men and women [35]. The purpose of this study was to assess the spectrum of psychosocial dysfunction in a group of outpatients with treatment resistant depression. We hypothesized that this sample of patients would be experiencing low levels of psychosocial functioning across multiple domains. 2. Subjects and methods 2.1. Patient selection and study design Subjects were recruited at the Depression Clinical and Research Program (DCRP) of Massachusetts General Hospi-
197
tal (MGH) for the purposes of a 6-week, double-blind, placebo-controlled trial to assess the efficacy of lithium (Li) augmentation of nortriptyline (NT) for subjects with TRD who had previously failed a 6-week open trial of NT. The data presented in this paper were collected during the screening visit for the open phase of the study. Subjects were recruited through clinical referrals and advertisement. In the latter case, prospective participants responded to newspaper and radio advertisements. These advertisements listed common symptoms of depression and instructed respondents to leave a message at a central phone number if they believed they were experiencing any of these symptoms. Prospective participants who had been referred by other clinicians or had responded to the advertisement were scheduled for a screen visit. The screen visits were conducted by one of the staff psychiatrists or psychologists at the Massachusetts General Hospital Depression Clinical and Research Program (DCRP), all of whom were trained in the use of all scales involved in this study. During the screen visit a structured clinical interview was conducted and a formal determination was made as to the patient’s eligibility for the study. A total of 92 outpatients were enrolled. Inclusion criteria were as follows: men and women ages 18–70 with major depressive disorder (MDD) diagnosed using the Structured Clinical Interview for the DSM-III-R—Patient Edition [39], and a score on the 17-item Hamilton Depression Rating Scale [11] greater than or equal to 18. Treatment resistance was defined as at least one, but no more than five adequate failed trials during the current depressive episode. An adequate trial was defined with the use of the Harvard Antidepressant Treatment History Form [26], which provides specific criteria for the dose and length of a trial to be considered adequate. Exclusion criteria for this trial were defined as follows: bipolar I or II disorder, psychosis, a history of organic mental or seizure disorder, serious or unstable medical illness, substance abuse disorders active within the past 12 months, acute suicidal risk (as assessed through clinical interview and using the HAM-D-17), pregnancy, lactation, history of adverse reaction or allergy to the study medications, concomitant use of psychotropic medications, and clinical or laboratory evidence of thyroid abnormalities. Participants in this study signed an Institutional Review Board (IRB) approved informed consent during the screen visit. 2.2. Measurement of psychosocial functioning Several scales have been developed to measure psychosocial functioning [41]. The Longitudinal Interval Follow-up Evaluation (LIFE) scale was developed during the National Institute for Mental Health (NIMH) collaborative study of the psychobiology of depression [15]. It provides an organized and comprehensive method to record the retrospective and prospective course of illness and treatment. The advantages of the LIFE scale are that it is established and reliable, especially for retrospective assessment of treatment history [17].
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In the present study, the LIFE sub-scale for psychosocial functioning was administered during the screen visit. This clinician-administered sub-scale contains a section designed to measure psychosocial functioning in five specific domains—work, interpersonal relations, sexual functioning, overall satisfaction and recreation. The first three of these domains contain sub-domains as follows: Domain Work Interpersonal relations Sexual functioning
Sub-domains Employment, household duties, student wo rk Spouse, children, other relatives, friends Enjoyment, frequency
In addition, our study focused on three additional items. Two of these represent a patient and a clinician rated item focusing on the global assessment of social adjustment. The last item represents a clinician rating of the reliability of the information gathered for the LIFE assessment. Each of the five LIFE domains and two global assessment items are scored on a five point scale, with (1) representing a high level of functioning (very good), (2) satisfactory functioning (good), (3) mild impairment (fair functioning), (4) moderate impairment (poor functioning), and (5) severe impairment (very poor functioning). For each domain and item, two scores are assigned—one reflecting function during the past month and a second score reflecting best functioning during the past 5 years. For the item reflecting the rater’s assessment of reliability and completeness of the information gathered, a five point scale is used as follows: 1, very good, 2, good, 3, only fair, 4, poor, and 5, very poor. For the current study, we examined the LIFE domain and item scores obtained during the screen visit that reflect function both during the past month, and best functioning during the past 5 years.
Table 1 Longitudinal Internal Follow-up Evaluation (LIFE) scale scores Work Employment Hours/week last month Hours/week last 5 years Impairment last month Impairment last 5 years Household duties Impairment last month Impairment last 5 years Student work Impairment last month Impairment last 5 years
19.1 27.6 3.2 1.8 3.1 1.8 3.6 2.4
Interpersonal relations Spouse last month Spouse last 5 years Children last month Children last 5 years Relatives last month Relatives last 5 years Friends last month Friends last 5 years
2.6 2.1 2.2 1.7 3 2.7 3.1 2.1
Sexual functioning Enjoyment last month Enjoyment last 5 years Frequency last month Frequency last 5 years
2.7 2.5 4 2.7
Overall satisfaction Satisfaction last month Satisfaction last 5 years
4.2 2.7
Recreation Recreation last month Recreation last 5 years
4 2.3
Descriptive analyses for continuous and nominal variables were used to characterize the LIFE subscale for psychosocial functioning scores in this sample.
Patient global assessment of social adjustment Last month Last 5 years
4.5 2.9
3. Results
Clinician global assessment of social adjustment Last month Last 5 years
4.4 2.7
Overall social adjustment
1.4
2.3. Statistical analysis
The mean age of our sample (n = 92) was 41.1 ± 11.7 years; 90% were Caucasian; 50% were female; 73% were single; 52% were employed; and 47% were college educated. The mean age of onset of depression was 22.4 ± 14.1 years, the mean duration of the current depressive episode was 96.2 ± 114.4 months and the mean baseline HAM-D-17 score was 21.3 ± 3.9. The mean NT dose and blood levels at week 6 of the open trial were 121.2 ± 33.7 mg and 101.0 ± 50.5 ng/ml, respectively. For all patients, the mean number of failed trials during the current major depressive episode was 2.3 ± 1.5. Table 1 presents the LIFE domain/item scores for the entire sample. Of note are the following findings. When rating patient functioning during the last month, clinicians
Rating scale: 1, very good functioning; 2, good functioning; 3, mild impairment; 4, moderate impairment; 5, severe impairment.
report mild to moderate impairment in work related activities (formal employment, household duties, and student work), good to fair interpersonal relations (spouse, children, relatives, and friends), a poor level of involvement in recreational activities and mild impairment of ability to enjoy sexual activity. In contrast to these findings, patient and clinician global assessment of social adjustment were assigned moderate/marked impairment and poor to very poor ratings. In addition, clinicians report of patient global satisfaction (contentment and gratification) received a poor to very poor
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rating. Reliability of information gathered was assigned a very good to good rating. When comparing functioning during the last month with best functioning during the last 5 years, it is clear that current functioning was rated as significantly worse. The range of difference in functioning between these two time frames was 0.2–1.7 (points on the LIFE scale).
4. Discussion To our knowledge, this is the first study to report on measures of psychosocial functioning in a sample of depressed patients formally defined as treatment resistant. Results indicate that clinicians rated patients’ functioning during the last month as mild to moderately impaired in several specific areas (work activities, interpersonal relations, and sexual relations) and as moderately to severely impaired in recreational activities. When examining global ratings of functioning, raters and patients evidenced a tendency to assign lower ratings of functioning (moderate/marked impairment or poor/very poor). In addition we found a significant contrast between ratings of current functioning and ratings of best functioning within the last 5 years, with the former receiving lower ratings. The discrepancy between specific and global ratings of functioning could be accounted for by a tendency for patients to assign lower ratings when a global question is posed. We are not aware of any previous studies that have evaluated this phenomenon. However, previous research does suggest that, when in the midst of a depressive episode, patients have the tendency to make negative, global attributions [2]. In addition, a key concept in the conceptualization of depression by cognitive therapists is distorted thinking. Cognitive distortions that relate to this tendency of assigning negative global ratings are “all or none thinking” and catastrophizing. Clinical experience also suggests that patients readily assign very global descriptions to their functioning (i.e. clinician asks “how have you been feeling?” and the patient responds “terribly”), but when pressed to describe functioning in specific domains a more mixed pattern is observed. Thus, the cognitive style associated with depression (that has been empirically validated) could directly contribute to the phenomenon we describe above. Clinicians, during the screening visit for this protocol, gathered very detailed information about chronic symptoms and past ineffective treatments. It is possible that a global picture of patient distress emerged during this process that influenced assignment of global ratings of psychosocial functioning. The primary strengths of this study were the use of structured interview instruments including the SCID-P, HAM-D17, and LIFE scale, and formal definition of treatment resistance (using the HATH). The latter resulted in a patient sample with well-characterized treatment resistant unipolar depression. One limitation of this study is the effect of depressive state on patients’ report of psychosocial functioning.
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During the midst of a major depressive episode patients may evidence the tendency to over report functional impairment, although in this case global ratings were probably affected in this way more than specific ratings. Another limitation of the study is that the LIFE scale does not provide a convention for higher order scale scores in the psychosocial domains measured; rather, we report LIFE psychosocial functioning subscale scores. Our method, however, is consistent with both a recent, prominent article [38] in which these scores are reported in the same manner and an article written by the original author of the LIFE scale [15] where no other convention is suggested. Also, we do not report standard deviations for any mean scores of the five-point Likert scale. With respect to ceiling and/or floor effects, few mean scores for our sample’s LIFE psychosocial functioning scales are at either extreme of the five-point Likert scale. Thus, we do not feel a ceiling or floor effect is of any significance. An additional limitation of the study is the exclusion criteria used. Because of these criteria, this sample may not represent treatment resistant patients in general, and in turn, typical levels of psychosocial functioning found in this population. It is reasonable to believe that significantly more psychiatric or medical comorbidity could lower levels of functioning considerably, and have changed our results. As a final note, the average duration of the current major depressive episode for this sample was unusually long –96.2 ± 114.4 months. Because of this, it is possible that level of functioning was not reflective of an acute depressive episode, but rather of a chronic episode. Perhaps more acute impairment was evidenced at the onset of the episode and then moderated after such a lengthy period of time. Patients with such protracted episodes may learn coping skills that allow them to function better in the areas that are measured by the LIFE subscale of psychosocial functioning. The results of this study suggest the need for more careful assessment of psychosocial functioning within the treatmentresistant depressed patient population. Assessment of such functioning can clearly guide treatment efforts. As an example, after careful assessment with an instrument such as the LIFE, a psychotherapist could more easily identify, with the patient, specific target areas to focus on in treatment. In addition, such an assessment process could allow a psychopharmacologist to select medications that would target symptoms associated with the particular problem area (e.g. irritability associated with marital conflict). Finally, proper assessment of psychosocial functioning and appropriate treatment modifications is in line with a recent emphasis in the literature regarding achieving full remission from the disorder rather than simply response. Available evidence suggests that achieving full remission confers a better longterm prognosis for patients who have suffered with depression. Future research is needed to elucidate the impact of treatment resistance on psychosocial functioning. Results of the ongoing NIMH-funded Sequenced Treatment Alternatives to Relieve Depression (STARD) trial will prove helpful in this regard.
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5. Conclusion To our knowledge, this is the first study to assess psychosocial functioning in a sample of patients formally defined as treatment resistant. Results suggest that clinicians rated patients’ functioning during the last month as mild to moderately impaired in several specific areas (work activities, interpersonal relations, and sexual relations) and as moderately to severely impaired in recreational activities. When examining global ratings of functioning, raters and patients evidenced a tendency to assign lower ratings of functioning (moderate/ marked impairment or poor/very poor). Future research is needed to elucidate the impact of treatment resistance on psychosocial functioning.
Acknowledgements Supported in part by NIMH grant R29 MH46952 (AAN).
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