# 2008 The Authors Journal compilation # 2008 Blackwell Munksgaard
Acta Neuropsychiatrica 2008: 20: 300–306 All rights reserved DOI: 10.1111/j.1601-5215.2008.00339.x
ACTA NEUROPSYCHIATRICA
Functional impairment and previous suicide attempts in bipolar disorder Rosa AR, Franco C, Martı´ nez-Aran A, Sa´nchez-Moreno J, Salamero M, Valenti M, Tabare´s-Seisdedos R, Gonza´lez-Pinto A, Kapczinski F, Vieta E. Functional impairment and previous suicide attempts in bipolar disorder. Objective: The aim of the present study was to assess the association between previous suicide attempts and functional impairment among euthymic patients with bipolar disorder (BD). Methods: Seventy-one Diagnostic Statistical Manual IV (DSM-IV) patients with BD and 61 healthy volunteers were recruited from the Bipolar Disorder Program at the Clinic Hospital of Barcelona. Patients with (n ¼ 36, 50.7%) and without (n ¼ 35, 49.3%) previous suicide attempts were assessed using the Structured Clinical Interview for DSMIV-TR (SCID-P). Previous suicide attempts were carefully investigated by means of patient and caregiver interview and by a standard structured interview from the protocol of our BD Program. The Functioning Assessment Short Test (FAST) was employed to assess functional impairment. Results: Euthymic patients with previous suicide attempts showed functional impairment, particularly in occupational (F ¼ 30.39; p ¼ 0.001) and cognitive functioning (F ¼ 18.43; p ¼ 0.001). In addition, family history of psychiatric illness (w2: 6.49; degrees of freedom (df) ¼ 2;132; p ¼ 0.010), family history of affective disorders (w2 ¼ 5.57; p ¼ 0.017), psychotic symptoms (w2 ¼ 5.88; p ¼ 0.014) and axis II comorbidity were associated with previous suicide attempts (w2 ¼ 5.16; p ¼ 0.021). Conclusion: Bipolar patients with previous suicide attempts had lower overall functioning than patients who did not attempt suicide. Previous suicide attempts were particularly associated with the occupational and cognitive domains of functioning.
Introduction
Bipolar disorder (BD) is a prevalent, often severe and disabling illness with elevated lethality, mostly due to suicide (1). BD is associated with a significant risk of attempted suicide (2). During their lifetime, 80% of patients with BD exhibit suicidal behaviour and 51% attempt suicide (3). Suicide rate among BD patients averages approximately 1% annually and is about 60 times higher than the general population rate (4). The higher lethality of suicide acts in BD translates into a much lower ratio of attempts/suicide (approximately 3:1) than in the general population (approximately 30:1) (4). It has been described that the acute phases of the illness, especially, depressive and mixed states are associated with suicidal behaviour (5–8). Furthermore, previous studies found that the depressive 300
Adriane R. Rosa1,2, Carolina Franco2,3, Anabel MartnezAran2, Jose Sa´nchez-Moreno2,4, Manel Salamero2, M. Valenti2, Rafael Tabare´s-Seisdedos5, Ana Gonza´lez-Pinto6, Fla´vio Kapczinski1, Eduard Vieta2 1 Bpolar Disorders Program, Molecular Psychiatry Laboratory, Hospital de Clinicas de Porto Alegre, Ramiro Barcelos, Porto Alegre, RS, Brazil; 2Bipolar Disorders Program, Clinical Institute of Neuroscience, Hospital Clinic of Barcelona, CIBERSAM, Villarroel, Barcelona, Spain; 3Department of Psychiatry, Hospital General Universitario Gregorio Maran˜o´n, CIBERSAM, Madrid, Spain; 4Department of Psychiatry, Universidad Autonoma de Madrid Hospital, Universitario de la Princesa, CIBERSAM, Madrid, Spain; 5Teaching Unit of Psychiatry and Psychological Medicine, Department of Medicine, University of Valencia, CIBERSAM, Spain; and 6Department of Psychiatry, Santiago Apostol Hospital, Osakidetza Mental Health System, CIBERSAM, Vitoria, Spain
Keywords: bipolar disorder; cognition; functioning; occupational functioning; suicide attempts Eduard Vieta, Bipolar Disorders Program, Clinical Institute of Neuroscience, University Clinic Hospital of Barcelona, Villarroel 170, 08036-Barcelona, Spain. Tel: 134932275401; Fax: 134932279876; E-mail: [email protected]
polarity (9) as well the concurrent depressive symptoms in mania (10) appear to be associated with suicidality in bipolar patients. In this context, lithium has been found to show antisuicidal properties and reduces lethality of suicidal acts among BD patients (11). But little is known about suicide behaviour and euthymic bipolar patients and its impact on daily living functioning partly because of the exclusion of suicidal patients from treatment trials (12). BD ranks as the sixth leading cause of disability worldwide according to the World Health Organization (13). In ageing samples, there is evidence of rates of disability comparable with those of patients with schizophrenia (14). It should be noted that the disability related to BD is not only restricted to the symptomatic phases (15–17). It has
Functional impairment and suicide in bipolar disorder been suggested that BD patients with previous suicide attempts are more predisposed to be functionally impaired (18,19). Specifically, cognitive functioning seems to be altered in patients with BD who attempted suicide (20,21). However, a number of studies on this issue show important limitations. A recent study showed an association between previous suicide attempts and functioning that emerged as a secondary finding (20). Another study found that the level of functioning was decreased in patients with chronic illness course, history of rapid cycling, suicidal behaviour, psychiatric and medical comorbidity. It is noteworthy that most studies carried out with a focus functioning have been performed using the Global Assessment of Functioning (GAF) scale (19). Despite the fact that the scale takes part of the DSM-IV assessment and is widely used, the assessment performed using the GAF has limitations. The original GAF instructions call for rating symptoms and overall functioning. But, it does not convey specific information about differential domains of functioning such as cognition, work and interpersonal relationships. The present study aims to assess whether previous suicide attempts are associated with lower functioning in a sample of well-defined, clinically euthymic BD patients compared with healthy controls. We have hypothesised that patients who experienced previous suicide attempts would have a lower psychosocial functioning. In addition, we have investigated whether variables related to the course of illness would present a differential impact in BD patients who had previous suicide attempts.
Material and methods Subjects
Patients. The sample was derived from the BD Program at the Hospital Clinic of Barcelona (n ¼ 71). Subjects gave written informed consent to participate in this study. Subjects who met the following criteria were included: 18 years or older, DSM-IV-TR criteria for bipolar affective disorder type I or II according to the Structured Clinical Interview for DSM-IV-TR (SCID-P) (22,23); being euthymic: 17-item Hamilton Depression Rating Scale (24) ,9 and a Young Mania Rating Scale Score (25) ,7 (26). Controls. Sixty-one healthy controls were screened through the SCID to exclude a past psychiatric history. This sample reported having no firstdegree relatives with BD or other psychiatric disorders in an interview before screening. This group was recruited from a pool of normal
volunteers who gave written informed consent to participate in this study. The study was approved by the Hospital Clinic of Barcelona Ethics Committee and was carried out in compliance with the Helsinki Declaration of 2004 (the Evaluation, Support and Prevention Unit). Methods
Diagnostic assessment. The SCID-P was administered by trained personnel to each subject for diagnosis. Previous suicide attempts were carefully investigated by means of both patient and caregiver interviews and data from the protocol of the BD Program. There were no relation between the time from the last suicide, type of suicide attempt and the day of the data recollection. The information registered on our protocol included clinical variables such as age of onset of BD, duration of illness, number of episodes (manic, depressive or mixed), number of hospitalisations, number of previous suicide attempts, type of suicide attempt (violent or not violent), severity of suicide attempt (high/low medical seriousness), psychotic symptoms, rapid cycling, current drugs abuse and family history of psychiatric and affective disorders. Axis II comorbidity was longitudinally assessed by a standard structured interview from the protocol of our BD Program. Outcome assessments. Functioning was evaluated by a trained research assistant using the FAST. It is a simple interviewer-administered instrument that provides an objective evaluation of the level of functioning in psychiatric patients, including bipolar patients for the past 15 days before assessment. The scale has shown strong psychometric properties (27). It is very easy to apply and requires a very short time to be administered (see Appendix). It comprises 24 items, which are divided among six specific areas of functioning: autonomy, occupational functioning, cognitive functioning, financial issues, interpersonal relationships and leisure time. Each item is rated using a 4-point scale. An item score of 0 indicates no difficulty, and a score 1 on any item indicates some degree of functional impairment in that domain. The FAST scale total score goes from 0 to 72. A total score of 72 represents the lowest possible functioning, and 0 represents the highest possible functioning with a cut-off point at .11. Statistical analysis
Group differences between the patients with previous suicide attempts, without previous suicide 301
Rosa et al. attempts and control sample were compared by means of chi-squared tests for dichotomous variables. The three groups were tested by in one-way ANOVA followed by Tukey post hoc comparison procedure when significant main effects were present for quantitative variables. Two-tailed p , 0.05 was required for statistical significance. All statistical analyses were performed using the SPSS version 12.0 software package.
Results
Our sample consisted of 34 women (47.9%) in the patient group and 37 in the control group (60.7%). The mean age of the patients was 45 years (median 44.99, SD: 13.50) and mean age of the controls was 49 years (median 49.16, SD: 17.74). Twenty-three (33.3%) patients and 17 (27.9%) healthy controls showed a high level of education; 41 (58.5%) patients and 51 (83.6%) in the control group were working. The other 10 (16.4%) healthy controls
were retired (p , 0.001). Clinical features such as a family history of psychiatric illness (w2 ¼ 6.49, p ¼ 0.010), family history of affective disorders (w2 ¼ 5.57; p ¼ 0.017), psychotic symptoms (w2 ¼ 5.88, p ¼ 0.014) and axis II comorbidity (w2 ¼ 5.16, p ¼ 0.021) were overrepresented in suicide attempters. Among all the patients with suicide attempts, in 9.3%, the methods were violent and in 11.9% of them, the suicide attempts were associated with high medical seriousness. There were no significant differences between the two groups with regard to the number of hospitalisations, number of total episodes, number of depressive episodes, depressive symptoms, number of manic episodes, number of mixed episodes and manic symptoms. The sociodemographic and clinical variables are shown in Table 1. Among the 71 bipolar patients, mood-stabilising agents were the most commonly prescribed agents (80.3%); 54.9% received antipsychotics, 26.8% antidepressants and 36.6% anxiolytic sedatives. Non-significant differences between the two groups
Table 1. Clinical and demographic characteristics in patients with/without previous suicide attempts and control group
Men Women Work situation Employed Unemployed Education University or post-graduate complete Primary or secondary school Family history of psychiatric illness Family history of affective disorders Suicide history family Drug abuse Psychotic symptoms Lifetime events Axis I comorbidity Axis II comorbidity Rapid cycling
Age Age of first hospitalisation Hospitalisations Manic episodes Mixed episodes Depressive episodes Hypomanic episodes Total episodes Duration of illness YMRS HAM-D
Total n (%)
With suicide attempts n (%)
Without suicide attempts n (%)
Control group n (%)
37 (52.1) 34 (47.9)
20 (54.1) 16 (47.1)
17 (45.9) 18 (52.9)
24 (39.3) 37 (60.7)
41 (58.5) 29 (41.5)
17 (41.4) 19 (65.5)
24 (58.6) 10 (34.5)
51 (83.6) 10 (16.4)
23 46 36 32 14 58 45 31 33 42 8
13 23 24 21 8 31 28 16 20 26 3
10 23 12 11 6 27 17 15 13 16 5
17 (27.9) 44 (72.1)
(33.3) (66.7) (53.7) (49.2) (20.6) (81.7) (64.3) (46.3) (46.5) (59.2) (11.6)
(56.5) (50.0) (66.7) (65.6) (57.1) (53.4) (62.2) (51.6) (60.6) (61.9) (37.5)
p value
2.48
0.29
14.29
0.001
1.03
0.67
6.49 5.57 0.23 0.95 5.88 0.13 2.42 5.16 0.63
0.010 0.017 0.43 0.25 0.014 0.46 0.094 0.021 0.34
Mean
SD
Mean
SD
Mean
SD
Mean
SD
F*
p value
44.99 25.25 1.37 2.73 0.35 5.23 3.82 11.89 17.88 1.07 2.08
13.50 17.28 1.53 3.88 0.91 6.42 11.36 15.20 10.95 2.07 3.31
43.94 26.80 1.67 3.71 0.48 5.46 1.61 11.17 18.37 1.14 2.17
9.43 12.66 1.88 4.78 1.16 5.19 2.41 8.68 9.60 1.82 3.81
46.06 23.52 1.11 1.85 0.24 5.04 5.77 12.71 17.36 1.00 2.00
16.79 21.40 1.13 2.66 0.60 7.41 15.3 20.35 12.35 2.33 2.76
49.16
17.74
0.69 0.51 1.74 3.03 0.82 0.05 1.67 0.17 0.14 0.08 0.04
0.50 0.48 0.19 0.09 0.37 0.82 0.20 0.69 0.71 0.78 0.83
HAM-D, Hamilton Depression Rating Scale; YMRS, Young Mania Rating Scale Score. *ANOVA. Statistically significant values are indicated in bold.
302
(43.5) (50.0) (33.3) (34.4) (42.9) (46.6) (37.8) (48.4) (39.4) (38.1) (62.5)
w2
Functional impairment and suicide in bipolar disorder (with or without suicide attempts) were found regarding the pharmacological treatment. Table 2 compares FAST total scores and subscores in patients with, without previous suicide attempts and the control group. Our data show that patients with previous suicide attempts had a higher FAST total score than patients without previous suicide attempts and control group (with suicide: mean 22.78, SD: 14.18; without suicide: mean 14.20, SD: 10.63; control: mean 6.07, SD: 4.72; p ¼ 0.001). In the patient group, the specific domains in which differences were identified were occupational functioning (with suicide: mean 8.81, SD: 6.66; without suicide: mean 4.43, SD: 5.65; control group: mean 1.08, SD: 1.99, p ¼ 0.001) and cognitive functioning (with suicide: 4.28, SD: 3.60; without suicide: mean 2.49, SD: 2.65, control: mean: 1.11, SD: 1.30, p ¼ 0.001).
Discussion Main findings
The present study showed that euthymic bipolar patients with previous suicide attempts had lower overall functioning, as assessed using the FAST scale compared with euthymic bipolar patients without suicide attempts. Occupational and cognitive functioning were significantly more impaired among patients who attempted suicide previously. Furthermore, we found that patients with previous suicide attempts had more psychotic symptoms, family history of psychiatric disorders and axis II comorbidity than patients without previous suicide attempts. The present study suggests that, in BD populations, it is important to consider clinical features such as family history of psychiatric and affective disorders whenever assessment of risk of suicide is concerned. Moreover, our findings also point out that familiar loading might also reflect the severity of illness, in the sense that it is
increased in the subgroup of patients who had already attempted suicide. Our findings are in line with previous studies, which showed that rates of psychosis were greater among patients with history of suicide (28,29). There is evidence pointing that past suicidal behaviour is perhaps the best predictor of future suicidal behaviour. In addition, other risk factors described in literature for non-fatal suicidal behaviour includes family history of suicide, early onset of BD, the total and extent of depressive previous episodes, increasing severity of affective episodes, psychosis, hopelessness, the presence of mixed affective states, rapid cycling, antidepressant-induced mania, comorbid axis I, II and III disorders and abuse of alcohol or drugs (2,30–32). The method for violent suicide behaviour is also associated with some particular characteristics such as age, marital status, affective disorder and psychiatric comorbidities (33,34). It is described that the rates of suicidal behaviour appear to be similar among BD I and BD II patients but the risk factors for it may differ somewhat between the two (3,33). Axis II comorbidity was associated with higher rates of previous suicide attempts as it has been described previously (35). Psychiatric comorbidity is often associated with early onset of bipolar symptoms, more severe course, poorer treatment compliance and worse outcomes related to suicide and other complications (36). Although comorbid personality disorders have a great impact on the course and outcome in BD, it has received little systematic study. Axis II comorbidity (30) is very common in BD and worsen the prognosis of the illness. It has been associated with lower recovery rates (37), greater unemployment (38), comorbid substance abuse (38,39) increased in the number of hospitalisation and suicide attempts, more vulnerability to stress factors and functioning outcomes measured by the GAF (40). Especially, cluster B personality disorder is a prevalent comorbid
Table 2. Functional impairment across different domains in bipolar patients with/without previous suicide attempts and control group
FAST total FAST autonomy FAST occupational FAST cognitive FAST interpersonal FAST financial issues FAST leisure time
With suicide attempts, n ¼ 37 (52.1%)
Without suicide attempts, n ¼ 34 (47.9%)
Control group, n ¼ 61
Mean
SD
Mean
SD
Mean
SD
F*
p value
Tukey post hoc
22.78 2.83 8.81 4.28 4.28 0.83 1.81
14.18 3.29 6.66 3.60 3.4 1.81 1.80
14.20 1.80 4.43 2.49 3.29 0.31 1.97
10.63 2.50 5.65 2.65 2.73 0.80 1.81
6.07 0.39 1.08 1.11 1.90 0.20 1.38
4.72 1.00 1.99 1.30 2.65 0.54 1.28
33.89 13.99 30.39 18.43 8.02 3.99 1.80
0.001 0.001 0.001 0.001 0.01 0.021 0.17
A.B.C A¼B; A, B.C A.B.C A.B.C A¼B; A.C; B¼C A¼B; A.C; B¼C
*ANOVA: significant differences at p , 0.05.
303
Rosa et al. condition identifiable in one third to one half of individuals with BD (41), making an independent contribution to an increased lifetime suicide risk (42). But, beyond that, patients presented more severe and chaotic prognosis of the disorder for several reasons. Poor treatment adherence is the rule, which may be related to higher rates of relapse (43,44) and higher rates of previous suicide attempts. Borderline personality disorder increases suicide risk among bipolar patients due to a contribution to impulsive aggression, which could reflect underlying central serotoninergic dysfunction (45); recent evidence shows that lithium treatment reduces both previous suicide attempts as well as the lethality of suicide acts among BD patients (4,11). One of the main strength of this study is that both the cognitive and occupational domains of FAST were found to be more severely impaired in euthymic patients with previous suicide attempts. Nowadays, in literature, it has been described that suicidality and previous suicide attempts may represent a marker of illness severity and may partly account for the functioning in euthymic bipolar patients, especially regarding cognitive and occupational areas (46,47). In fact, cognitive difficulties in BD patients, especially verbal memory dysfunctions, have been described as a good predictor of work impairment in euthymic patients and thus, poor psychosocial functioning (46,47). BD patients had problems in encoding and retrieving verbal information that might explain the impairment in daily functioning, even during remission of the illness (48). This further supports our findings because the cognitive and occupational domains seem to vary in a co-linear fashion (21,30). Furthermore, illness severity and cognitive impairment are not independent, so it is difficult to assess and discuss their respective influence in functional outcome (21). As suicidality and cognitive and functioning share the same factors, we might suppose that it stables as a circle. As much more the previous suicide attempts more the severity of the illness and worse the impairment in occupational and cognitive domains. In contrast with literature, we did not find any association between suicide attempts and depressive symptoms and hopelessness. Depression and hopelessness, comorbidity with substance use disorders (nicotine-related disorders) and preceding suicidal behaviour are key indicators of risk (49). The main reason for that finding is that our sample consists of euthymic patients. Hopelessness, comorbid personality disorder and previous suicide attempt have been described as independent risk factors for suicide attempts. Suicidal behav304
iour varied markedly between different phases of BD. Suicide attempts and suicidal ideations were related to acute phases that are associated with depressive aspects of the illness. Hopelessness and severity of depression were key indicators of risk in all phases as some authors point out (3,50,51). In this regard, our data might have an impact in the future evaluation of patient with BD. It is important to evaluate the risk of suicide and its impact on patient’s life despite an asymptomatic phase of the illness. Furthermore, the better the factors associated with suicidality are recognised the better the clinicians will be able to develop strategies to minimise the risk.
Conclusions
Psychosocial functioning, in particular cognitive and occupational functioning, is more impaired in bipolar patients with previous suicide attempts. Clinical features such as a family history of psychiatric illness, family history of affective disorders, lifetime psychotic symptoms and axis II comorbidity were associated with previous suicide attempts. Euthymic bipolar patients with previous suicide attempts might have a more severe course of the illness that may explain the marked functional impairment found in this group. An inner strength of this study is the fact that we used a scale tailored for BD patients to assess functioning. Our findings should be interpreted in the light of the fact that this was a naturalistic cross-sectional study that does not allow for assumptions of causality. We studied previous suicide attempts and not complete suicide. As the sample size was small, the power was not sufficient to detect less pronounced associations. Prospective studies are warranted to assess whether a causal relationship between functioning and previous suicide attempts can be ascertained.
Conflict of Interests
The author(s) declare that they have no competing interests related to this report. Eduard Vieta, has acted as a consultant, received grants or has been hired as a speaker by the following companies: Almirall, AstraZeneca, Bial, Bristol-Myers-Squibb, Eli Lilly, GlaxoSmithKline, Janssen-Cilag, Lundbeck, Merck Sharp & Dohme, Novartis, Organon, Otsuka, Pfizer, Sanofi Aventis, Servier, UCB. He has acted as consultant and has received grants from the Spanish Ministry of Health, Instituto de Salud Carlos III, CIBERSAM and from the Stanley Medical Research Institute.
Functional impairment and suicide in bipolar disorder Acknowledgements This work was supported by grants from the CAPES (Brazil), Spanish Ministry of Health, Instituto de Salud Carlos III, (FIS:PI050206), the Spanish Ministry of Health, Instituto de Salud Carlos III, CIBERSAM.
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Appendix. Functioning assessment short test. To what extent is the patient experiencing difficulties in the following aspects? Ask the patient about the areas of difficulty in functioning and score according to the following scale: (0): no difficulty, (1): mild difficulty, (2): moderate difficulty, (3): severe difficulty Autonomy 1. Taking responsibility for a household 2. Living on your own 3. Doing the shopping 4. Taking care of yourself (physical aspects, hygiene) Occupational functioning 5. Holding down a paid job 6. Accomplishing tasks as quickly as necessary 7. Working in the field in which you were educated 8. Occupational earnings 9. Managing the expected work load Cognitive functioning 10. Ability to concentrate on a book, film 11. Ability to make mental calculations 12. Ability to solve a problem adequately 13. Ability to remember newly-learned names 14. Ability to learn new information Financial issues 15. Managing your own money 16. Spending money in a balanced way Interpersonal relationships 17. Maintaining a friendship or friendships 18. Participating in social activities 19. Having good relationships with people close you 20. Living together with your family 21. Having satisfactory sexual relationships 22. Being able to defend your interests Leisure time 23. Doing exercise or participating in sport 24. Having hobbies or personal interests
(0) (0) (0) (0)
(1) (1) (1) (1)
(2) (2) (2) (2)
(3) (3) (3) (3)
(0) (0) (0) (0) (0)
(1) (1) (1) (1) (1)
(2) (2) (2) (2) (2)
(3) (3) (3) (3) (3)
(0) (0) (0) (0) (0)
(1) (1) (1) (1) (1)
(2) (2) (2) (2) (2)
(3) (3) (3) (3) (3)
(0) (1) (2) (3) (0) (1) (2) (3) (0) (0) (0) (0) (0) (0)
(1) (1) (1) (1) (1) (1)
(2) (2) (2) (2) (2) (2)
(3) (3) (3) (3) (3) (3)
(0) (1) (2) (3) (0) (1) (2) (3)
Acta Neuropsychiatrica 2008: 20: 300–306 All rights reserved DOI: 10.1111/j.1601-5215.2008.00339.x
ACTA NEUROPSYCHIATRICA
Functional impairment and previous suicide attempts in bipolar disorder Rosa AR, Franco C, Martı´ nez-Aran A, Sa´nchez-Moreno J, Salamero M, Valenti M, Tabare´s-Seisdedos R, Gonza´lez-Pinto A, Kapczinski F, Vieta E. Functional impairment and previous suicide attempts in bipolar disorder. Objective: The aim of the present study was to assess the association between previous suicide attempts and functional impairment among euthymic patients with bipolar disorder (BD). Methods: Seventy-one Diagnostic Statistical Manual IV (DSM-IV) patients with BD and 61 healthy volunteers were recruited from the Bipolar Disorder Program at the Clinic Hospital of Barcelona. Patients with (n ¼ 36, 50.7%) and without (n ¼ 35, 49.3%) previous suicide attempts were assessed using the Structured Clinical Interview for DSMIV-TR (SCID-P). Previous suicide attempts were carefully investigated by means of patient and caregiver interview and by a standard structured interview from the protocol of our BD Program. The Functioning Assessment Short Test (FAST) was employed to assess functional impairment. Results: Euthymic patients with previous suicide attempts showed functional impairment, particularly in occupational (F ¼ 30.39; p ¼ 0.001) and cognitive functioning (F ¼ 18.43; p ¼ 0.001). In addition, family history of psychiatric illness (w2: 6.49; degrees of freedom (df) ¼ 2;132; p ¼ 0.010), family history of affective disorders (w2 ¼ 5.57; p ¼ 0.017), psychotic symptoms (w2 ¼ 5.88; p ¼ 0.014) and axis II comorbidity were associated with previous suicide attempts (w2 ¼ 5.16; p ¼ 0.021). Conclusion: Bipolar patients with previous suicide attempts had lower overall functioning than patients who did not attempt suicide. Previous suicide attempts were particularly associated with the occupational and cognitive domains of functioning.
Introduction
Bipolar disorder (BD) is a prevalent, often severe and disabling illness with elevated lethality, mostly due to suicide (1). BD is associated with a significant risk of attempted suicide (2). During their lifetime, 80% of patients with BD exhibit suicidal behaviour and 51% attempt suicide (3). Suicide rate among BD patients averages approximately 1% annually and is about 60 times higher than the general population rate (4). The higher lethality of suicide acts in BD translates into a much lower ratio of attempts/suicide (approximately 3:1) than in the general population (approximately 30:1) (4). It has been described that the acute phases of the illness, especially, depressive and mixed states are associated with suicidal behaviour (5–8). Furthermore, previous studies found that the depressive 300
Adriane R. Rosa1,2, Carolina Franco2,3, Anabel MartnezAran2, Jose Sa´nchez-Moreno2,4, Manel Salamero2, M. Valenti2, Rafael Tabare´s-Seisdedos5, Ana Gonza´lez-Pinto6, Fla´vio Kapczinski1, Eduard Vieta2 1 Bpolar Disorders Program, Molecular Psychiatry Laboratory, Hospital de Clinicas de Porto Alegre, Ramiro Barcelos, Porto Alegre, RS, Brazil; 2Bipolar Disorders Program, Clinical Institute of Neuroscience, Hospital Clinic of Barcelona, CIBERSAM, Villarroel, Barcelona, Spain; 3Department of Psychiatry, Hospital General Universitario Gregorio Maran˜o´n, CIBERSAM, Madrid, Spain; 4Department of Psychiatry, Universidad Autonoma de Madrid Hospital, Universitario de la Princesa, CIBERSAM, Madrid, Spain; 5Teaching Unit of Psychiatry and Psychological Medicine, Department of Medicine, University of Valencia, CIBERSAM, Spain; and 6Department of Psychiatry, Santiago Apostol Hospital, Osakidetza Mental Health System, CIBERSAM, Vitoria, Spain
Keywords: bipolar disorder; cognition; functioning; occupational functioning; suicide attempts Eduard Vieta, Bipolar Disorders Program, Clinical Institute of Neuroscience, University Clinic Hospital of Barcelona, Villarroel 170, 08036-Barcelona, Spain. Tel: 134932275401; Fax: 134932279876; E-mail: [email protected]
polarity (9) as well the concurrent depressive symptoms in mania (10) appear to be associated with suicidality in bipolar patients. In this context, lithium has been found to show antisuicidal properties and reduces lethality of suicidal acts among BD patients (11). But little is known about suicide behaviour and euthymic bipolar patients and its impact on daily living functioning partly because of the exclusion of suicidal patients from treatment trials (12). BD ranks as the sixth leading cause of disability worldwide according to the World Health Organization (13). In ageing samples, there is evidence of rates of disability comparable with those of patients with schizophrenia (14). It should be noted that the disability related to BD is not only restricted to the symptomatic phases (15–17). It has
Functional impairment and suicide in bipolar disorder been suggested that BD patients with previous suicide attempts are more predisposed to be functionally impaired (18,19). Specifically, cognitive functioning seems to be altered in patients with BD who attempted suicide (20,21). However, a number of studies on this issue show important limitations. A recent study showed an association between previous suicide attempts and functioning that emerged as a secondary finding (20). Another study found that the level of functioning was decreased in patients with chronic illness course, history of rapid cycling, suicidal behaviour, psychiatric and medical comorbidity. It is noteworthy that most studies carried out with a focus functioning have been performed using the Global Assessment of Functioning (GAF) scale (19). Despite the fact that the scale takes part of the DSM-IV assessment and is widely used, the assessment performed using the GAF has limitations. The original GAF instructions call for rating symptoms and overall functioning. But, it does not convey specific information about differential domains of functioning such as cognition, work and interpersonal relationships. The present study aims to assess whether previous suicide attempts are associated with lower functioning in a sample of well-defined, clinically euthymic BD patients compared with healthy controls. We have hypothesised that patients who experienced previous suicide attempts would have a lower psychosocial functioning. In addition, we have investigated whether variables related to the course of illness would present a differential impact in BD patients who had previous suicide attempts.
Material and methods Subjects
Patients. The sample was derived from the BD Program at the Hospital Clinic of Barcelona (n ¼ 71). Subjects gave written informed consent to participate in this study. Subjects who met the following criteria were included: 18 years or older, DSM-IV-TR criteria for bipolar affective disorder type I or II according to the Structured Clinical Interview for DSM-IV-TR (SCID-P) (22,23); being euthymic: 17-item Hamilton Depression Rating Scale (24) ,9 and a Young Mania Rating Scale Score (25) ,7 (26). Controls. Sixty-one healthy controls were screened through the SCID to exclude a past psychiatric history. This sample reported having no firstdegree relatives with BD or other psychiatric disorders in an interview before screening. This group was recruited from a pool of normal
volunteers who gave written informed consent to participate in this study. The study was approved by the Hospital Clinic of Barcelona Ethics Committee and was carried out in compliance with the Helsinki Declaration of 2004 (the Evaluation, Support and Prevention Unit). Methods
Diagnostic assessment. The SCID-P was administered by trained personnel to each subject for diagnosis. Previous suicide attempts were carefully investigated by means of both patient and caregiver interviews and data from the protocol of the BD Program. There were no relation between the time from the last suicide, type of suicide attempt and the day of the data recollection. The information registered on our protocol included clinical variables such as age of onset of BD, duration of illness, number of episodes (manic, depressive or mixed), number of hospitalisations, number of previous suicide attempts, type of suicide attempt (violent or not violent), severity of suicide attempt (high/low medical seriousness), psychotic symptoms, rapid cycling, current drugs abuse and family history of psychiatric and affective disorders. Axis II comorbidity was longitudinally assessed by a standard structured interview from the protocol of our BD Program. Outcome assessments. Functioning was evaluated by a trained research assistant using the FAST. It is a simple interviewer-administered instrument that provides an objective evaluation of the level of functioning in psychiatric patients, including bipolar patients for the past 15 days before assessment. The scale has shown strong psychometric properties (27). It is very easy to apply and requires a very short time to be administered (see Appendix). It comprises 24 items, which are divided among six specific areas of functioning: autonomy, occupational functioning, cognitive functioning, financial issues, interpersonal relationships and leisure time. Each item is rated using a 4-point scale. An item score of 0 indicates no difficulty, and a score 1 on any item indicates some degree of functional impairment in that domain. The FAST scale total score goes from 0 to 72. A total score of 72 represents the lowest possible functioning, and 0 represents the highest possible functioning with a cut-off point at .11. Statistical analysis
Group differences between the patients with previous suicide attempts, without previous suicide 301
Rosa et al. attempts and control sample were compared by means of chi-squared tests for dichotomous variables. The three groups were tested by in one-way ANOVA followed by Tukey post hoc comparison procedure when significant main effects were present for quantitative variables. Two-tailed p , 0.05 was required for statistical significance. All statistical analyses were performed using the SPSS version 12.0 software package.
Results
Our sample consisted of 34 women (47.9%) in the patient group and 37 in the control group (60.7%). The mean age of the patients was 45 years (median 44.99, SD: 13.50) and mean age of the controls was 49 years (median 49.16, SD: 17.74). Twenty-three (33.3%) patients and 17 (27.9%) healthy controls showed a high level of education; 41 (58.5%) patients and 51 (83.6%) in the control group were working. The other 10 (16.4%) healthy controls
were retired (p , 0.001). Clinical features such as a family history of psychiatric illness (w2 ¼ 6.49, p ¼ 0.010), family history of affective disorders (w2 ¼ 5.57; p ¼ 0.017), psychotic symptoms (w2 ¼ 5.88, p ¼ 0.014) and axis II comorbidity (w2 ¼ 5.16, p ¼ 0.021) were overrepresented in suicide attempters. Among all the patients with suicide attempts, in 9.3%, the methods were violent and in 11.9% of them, the suicide attempts were associated with high medical seriousness. There were no significant differences between the two groups with regard to the number of hospitalisations, number of total episodes, number of depressive episodes, depressive symptoms, number of manic episodes, number of mixed episodes and manic symptoms. The sociodemographic and clinical variables are shown in Table 1. Among the 71 bipolar patients, mood-stabilising agents were the most commonly prescribed agents (80.3%); 54.9% received antipsychotics, 26.8% antidepressants and 36.6% anxiolytic sedatives. Non-significant differences between the two groups
Table 1. Clinical and demographic characteristics in patients with/without previous suicide attempts and control group
Men Women Work situation Employed Unemployed Education University or post-graduate complete Primary or secondary school Family history of psychiatric illness Family history of affective disorders Suicide history family Drug abuse Psychotic symptoms Lifetime events Axis I comorbidity Axis II comorbidity Rapid cycling
Age Age of first hospitalisation Hospitalisations Manic episodes Mixed episodes Depressive episodes Hypomanic episodes Total episodes Duration of illness YMRS HAM-D
Total n (%)
With suicide attempts n (%)
Without suicide attempts n (%)
Control group n (%)
37 (52.1) 34 (47.9)
20 (54.1) 16 (47.1)
17 (45.9) 18 (52.9)
24 (39.3) 37 (60.7)
41 (58.5) 29 (41.5)
17 (41.4) 19 (65.5)
24 (58.6) 10 (34.5)
51 (83.6) 10 (16.4)
23 46 36 32 14 58 45 31 33 42 8
13 23 24 21 8 31 28 16 20 26 3
10 23 12 11 6 27 17 15 13 16 5
17 (27.9) 44 (72.1)
(33.3) (66.7) (53.7) (49.2) (20.6) (81.7) (64.3) (46.3) (46.5) (59.2) (11.6)
(56.5) (50.0) (66.7) (65.6) (57.1) (53.4) (62.2) (51.6) (60.6) (61.9) (37.5)
p value
2.48
0.29
14.29
0.001
1.03
0.67
6.49 5.57 0.23 0.95 5.88 0.13 2.42 5.16 0.63
0.010 0.017 0.43 0.25 0.014 0.46 0.094 0.021 0.34
Mean
SD
Mean
SD
Mean
SD
Mean
SD
F*
p value
44.99 25.25 1.37 2.73 0.35 5.23 3.82 11.89 17.88 1.07 2.08
13.50 17.28 1.53 3.88 0.91 6.42 11.36 15.20 10.95 2.07 3.31
43.94 26.80 1.67 3.71 0.48 5.46 1.61 11.17 18.37 1.14 2.17
9.43 12.66 1.88 4.78 1.16 5.19 2.41 8.68 9.60 1.82 3.81
46.06 23.52 1.11 1.85 0.24 5.04 5.77 12.71 17.36 1.00 2.00
16.79 21.40 1.13 2.66 0.60 7.41 15.3 20.35 12.35 2.33 2.76
49.16
17.74
0.69 0.51 1.74 3.03 0.82 0.05 1.67 0.17 0.14 0.08 0.04
0.50 0.48 0.19 0.09 0.37 0.82 0.20 0.69 0.71 0.78 0.83
HAM-D, Hamilton Depression Rating Scale; YMRS, Young Mania Rating Scale Score. *ANOVA. Statistically significant values are indicated in bold.
302
(43.5) (50.0) (33.3) (34.4) (42.9) (46.6) (37.8) (48.4) (39.4) (38.1) (62.5)
w2
Functional impairment and suicide in bipolar disorder (with or without suicide attempts) were found regarding the pharmacological treatment. Table 2 compares FAST total scores and subscores in patients with, without previous suicide attempts and the control group. Our data show that patients with previous suicide attempts had a higher FAST total score than patients without previous suicide attempts and control group (with suicide: mean 22.78, SD: 14.18; without suicide: mean 14.20, SD: 10.63; control: mean 6.07, SD: 4.72; p ¼ 0.001). In the patient group, the specific domains in which differences were identified were occupational functioning (with suicide: mean 8.81, SD: 6.66; without suicide: mean 4.43, SD: 5.65; control group: mean 1.08, SD: 1.99, p ¼ 0.001) and cognitive functioning (with suicide: 4.28, SD: 3.60; without suicide: mean 2.49, SD: 2.65, control: mean: 1.11, SD: 1.30, p ¼ 0.001).
Discussion Main findings
The present study showed that euthymic bipolar patients with previous suicide attempts had lower overall functioning, as assessed using the FAST scale compared with euthymic bipolar patients without suicide attempts. Occupational and cognitive functioning were significantly more impaired among patients who attempted suicide previously. Furthermore, we found that patients with previous suicide attempts had more psychotic symptoms, family history of psychiatric disorders and axis II comorbidity than patients without previous suicide attempts. The present study suggests that, in BD populations, it is important to consider clinical features such as family history of psychiatric and affective disorders whenever assessment of risk of suicide is concerned. Moreover, our findings also point out that familiar loading might also reflect the severity of illness, in the sense that it is
increased in the subgroup of patients who had already attempted suicide. Our findings are in line with previous studies, which showed that rates of psychosis were greater among patients with history of suicide (28,29). There is evidence pointing that past suicidal behaviour is perhaps the best predictor of future suicidal behaviour. In addition, other risk factors described in literature for non-fatal suicidal behaviour includes family history of suicide, early onset of BD, the total and extent of depressive previous episodes, increasing severity of affective episodes, psychosis, hopelessness, the presence of mixed affective states, rapid cycling, antidepressant-induced mania, comorbid axis I, II and III disorders and abuse of alcohol or drugs (2,30–32). The method for violent suicide behaviour is also associated with some particular characteristics such as age, marital status, affective disorder and psychiatric comorbidities (33,34). It is described that the rates of suicidal behaviour appear to be similar among BD I and BD II patients but the risk factors for it may differ somewhat between the two (3,33). Axis II comorbidity was associated with higher rates of previous suicide attempts as it has been described previously (35). Psychiatric comorbidity is often associated with early onset of bipolar symptoms, more severe course, poorer treatment compliance and worse outcomes related to suicide and other complications (36). Although comorbid personality disorders have a great impact on the course and outcome in BD, it has received little systematic study. Axis II comorbidity (30) is very common in BD and worsen the prognosis of the illness. It has been associated with lower recovery rates (37), greater unemployment (38), comorbid substance abuse (38,39) increased in the number of hospitalisation and suicide attempts, more vulnerability to stress factors and functioning outcomes measured by the GAF (40). Especially, cluster B personality disorder is a prevalent comorbid
Table 2. Functional impairment across different domains in bipolar patients with/without previous suicide attempts and control group
FAST total FAST autonomy FAST occupational FAST cognitive FAST interpersonal FAST financial issues FAST leisure time
With suicide attempts, n ¼ 37 (52.1%)
Without suicide attempts, n ¼ 34 (47.9%)
Control group, n ¼ 61
Mean
SD
Mean
SD
Mean
SD
F*
p value
Tukey post hoc
22.78 2.83 8.81 4.28 4.28 0.83 1.81
14.18 3.29 6.66 3.60 3.4 1.81 1.80
14.20 1.80 4.43 2.49 3.29 0.31 1.97
10.63 2.50 5.65 2.65 2.73 0.80 1.81
6.07 0.39 1.08 1.11 1.90 0.20 1.38
4.72 1.00 1.99 1.30 2.65 0.54 1.28
33.89 13.99 30.39 18.43 8.02 3.99 1.80
0.001 0.001 0.001 0.001 0.01 0.021 0.17
A.B.C A¼B; A, B.C A.B.C A.B.C A¼B; A.C; B¼C A¼B; A.C; B¼C
*ANOVA: significant differences at p , 0.05.
303
Rosa et al. condition identifiable in one third to one half of individuals with BD (41), making an independent contribution to an increased lifetime suicide risk (42). But, beyond that, patients presented more severe and chaotic prognosis of the disorder for several reasons. Poor treatment adherence is the rule, which may be related to higher rates of relapse (43,44) and higher rates of previous suicide attempts. Borderline personality disorder increases suicide risk among bipolar patients due to a contribution to impulsive aggression, which could reflect underlying central serotoninergic dysfunction (45); recent evidence shows that lithium treatment reduces both previous suicide attempts as well as the lethality of suicide acts among BD patients (4,11). One of the main strength of this study is that both the cognitive and occupational domains of FAST were found to be more severely impaired in euthymic patients with previous suicide attempts. Nowadays, in literature, it has been described that suicidality and previous suicide attempts may represent a marker of illness severity and may partly account for the functioning in euthymic bipolar patients, especially regarding cognitive and occupational areas (46,47). In fact, cognitive difficulties in BD patients, especially verbal memory dysfunctions, have been described as a good predictor of work impairment in euthymic patients and thus, poor psychosocial functioning (46,47). BD patients had problems in encoding and retrieving verbal information that might explain the impairment in daily functioning, even during remission of the illness (48). This further supports our findings because the cognitive and occupational domains seem to vary in a co-linear fashion (21,30). Furthermore, illness severity and cognitive impairment are not independent, so it is difficult to assess and discuss their respective influence in functional outcome (21). As suicidality and cognitive and functioning share the same factors, we might suppose that it stables as a circle. As much more the previous suicide attempts more the severity of the illness and worse the impairment in occupational and cognitive domains. In contrast with literature, we did not find any association between suicide attempts and depressive symptoms and hopelessness. Depression and hopelessness, comorbidity with substance use disorders (nicotine-related disorders) and preceding suicidal behaviour are key indicators of risk (49). The main reason for that finding is that our sample consists of euthymic patients. Hopelessness, comorbid personality disorder and previous suicide attempt have been described as independent risk factors for suicide attempts. Suicidal behav304
iour varied markedly between different phases of BD. Suicide attempts and suicidal ideations were related to acute phases that are associated with depressive aspects of the illness. Hopelessness and severity of depression were key indicators of risk in all phases as some authors point out (3,50,51). In this regard, our data might have an impact in the future evaluation of patient with BD. It is important to evaluate the risk of suicide and its impact on patient’s life despite an asymptomatic phase of the illness. Furthermore, the better the factors associated with suicidality are recognised the better the clinicians will be able to develop strategies to minimise the risk.
Conclusions
Psychosocial functioning, in particular cognitive and occupational functioning, is more impaired in bipolar patients with previous suicide attempts. Clinical features such as a family history of psychiatric illness, family history of affective disorders, lifetime psychotic symptoms and axis II comorbidity were associated with previous suicide attempts. Euthymic bipolar patients with previous suicide attempts might have a more severe course of the illness that may explain the marked functional impairment found in this group. An inner strength of this study is the fact that we used a scale tailored for BD patients to assess functioning. Our findings should be interpreted in the light of the fact that this was a naturalistic cross-sectional study that does not allow for assumptions of causality. We studied previous suicide attempts and not complete suicide. As the sample size was small, the power was not sufficient to detect less pronounced associations. Prospective studies are warranted to assess whether a causal relationship between functioning and previous suicide attempts can be ascertained.
Conflict of Interests
The author(s) declare that they have no competing interests related to this report. Eduard Vieta, has acted as a consultant, received grants or has been hired as a speaker by the following companies: Almirall, AstraZeneca, Bial, Bristol-Myers-Squibb, Eli Lilly, GlaxoSmithKline, Janssen-Cilag, Lundbeck, Merck Sharp & Dohme, Novartis, Organon, Otsuka, Pfizer, Sanofi Aventis, Servier, UCB. He has acted as consultant and has received grants from the Spanish Ministry of Health, Instituto de Salud Carlos III, CIBERSAM and from the Stanley Medical Research Institute.
Functional impairment and suicide in bipolar disorder Acknowledgements This work was supported by grants from the CAPES (Brazil), Spanish Ministry of Health, Instituto de Salud Carlos III, (FIS:PI050206), the Spanish Ministry of Health, Instituto de Salud Carlos III, CIBERSAM.
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Appendix. Functioning assessment short test. To what extent is the patient experiencing difficulties in the following aspects? Ask the patient about the areas of difficulty in functioning and score according to the following scale: (0): no difficulty, (1): mild difficulty, (2): moderate difficulty, (3): severe difficulty Autonomy 1. Taking responsibility for a household 2. Living on your own 3. Doing the shopping 4. Taking care of yourself (physical aspects, hygiene) Occupational functioning 5. Holding down a paid job 6. Accomplishing tasks as quickly as necessary 7. Working in the field in which you were educated 8. Occupational earnings 9. Managing the expected work load Cognitive functioning 10. Ability to concentrate on a book, film 11. Ability to make mental calculations 12. Ability to solve a problem adequately 13. Ability to remember newly-learned names 14. Ability to learn new information Financial issues 15. Managing your own money 16. Spending money in a balanced way Interpersonal relationships 17. Maintaining a friendship or friendships 18. Participating in social activities 19. Having good relationships with people close you 20. Living together with your family 21. Having satisfactory sexual relationships 22. Being able to defend your interests Leisure time 23. Doing exercise or participating in sport 24. Having hobbies or personal interests
(0) (0) (0) (0)
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