Psychiatry Research ∎ (∎∎∎∎) ∎∎∎–∎∎∎
Contents lists available at ScienceDirect
Psychiatry Research journal homepage: www.elsevier.com/locate/psychres
A 2-year follow-up study of discharged psychiatric patients with bipolar disorder Chunyang Li, Chao Chen n, Bin Qiu, Guang Yang Department of Psychiatry, WuZhongpei Memorial Hospital, No. 3 Jianmin Road, Daliang Town, Shunde District of Foshan City, Guangdong 528300, China
art ic l e i nf o
a b s t r a c t
Article history: Received 24 January 2014 Received in revised form 31 March 2014 Accepted 9 April 2014
This study investigated medication compliance, disease recurrence and the recovery of social function in discharged psychiatric patients with bipolar disorder. A 2-year follow-up was conducted on all patients with bipolar disorder, who were hospitalized in our psychiatric department between June 2010 and May 2011. Risk factors for recurrence were analyzed based on a self-designed questionnaire. Of the 252 patients in the study, 210 had complete information (83.3%) for the 2-year follow-up: 170 cases of bipolar I disorder and 40 cases of bipolar II disorder. The 1-year and 2-year full-compliance rates were 41.0% and 35.7%, respectively. The 1-year and 2-year recurrence rates were 42.4% and 61.0%, respectively. Statistically significant differences in rates were found between the bipolar subtypes for 1-year full compliance, 1-year non-compliance, 2-year recurrence, and 2-year readmission. Logistic regression identified different sets of independent variables that were risk factors for recurrence, and protective factors for recurrence at 1 year and 2 years after hospital discharge. The results of the follow-up indicated that the situation of patients with bipolar disorder after discharge is not optimistic, because of high recurrence rates, high non-compliance rates and low recovery rates. Clinical and social experts should pay more attention to the situation. & 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Bipolar disorder Recurrence Medication compliance
1. Introduction Bipolar disorder is a common, disabling illness that is chronic and recurrent (Lin et al., 2006; Malhi et al., 2009; Leboyer and Kupfer, 2010). An early correct diagnosis of bipolar disorder, in conjunction with appropriate treatment, can contribute to an improved prognosis (Price and Marzani-Nissen, 2012; Cullen-Drill and Cullen-Dolce, 2008). Many recent studies have shown that pharmacotherapy and psychotherapy can help patients with bipolar disorder achieve remission and reduce relapse (Thase, 2008; Prasko et al., 2013). Although pharmacological and non-pharmacological treatments have made progress in treating bipolar disorder, the disorder often produces multiple relapses and impaired psychological functioning (Treuer and Tohen, 2010; Kupka and Regeer, 2007), and the overall prognosis of bipolar disorder does not appear to have been altered by such treatments (El-Mallakh et al., 2010). Medication non-adherence during the maintenance treatment of bipolar disorder is common, resulting in many adverse outcomes (Sajatovic et al., 2006; Bobo and Shelton, 2010). Given the correlation of non-adherence with high risk of relapse and hospitalization among bipolar disorder patients, it is important to improve medication
n
Corresponding author. Tel.: þ 86 757 2928 2895; fax: þ 86 757 2229 8820. E-mail address: [email protected] (C. Chen).
adherence for effective treatment (Depp et al., 2008). Many studies have shown that providing psycho-education to patients with bipolar disorder can increase medication adherence and prevent relapse (Sienaert and de Fruyt, 2008). We conducted a 2-year, follow-up study to investigate the degree of medication adherence and the recovery status of bipolar disorder patients discharged from a psychiatric hospital. The study was intended to provide relevant information that would contribute to improve prognosis and prevent relapse of bipolar disorder. This article summarizes the results of that study.
2. Methods 2.1. Patients The study sample consisted of patients who (1) were hospitalized for some time between June 2010 and May 2011 in our psychiatric department, and (2) were diagnosed with bipolar disorder, according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), by one attending physician and one associate chief physician. Patients were enrolled in the 2-year follow-up study regardless of their sex, age or subtype of bipolar disorder. All patients or their legal representatives signed informed consent before the patients entered the study. The study was approved by the Ethics Committee of WuZhongpei Memorial Hospital, Shunde District of Foshan City.
http://dx.doi.org/10.1016/j.psychres.2014.04.029 0165-1781/& 2014 Elsevier Ireland Ltd. All rights reserved.
Please cite this article as: Li, C., et al., A 2-year follow-up study of discharged psychiatric patients with bipolar disorder. Psychiatry Research (2014), http://dx.doi.org/10.1016/j.psychres.2014.04.029i
C. Li et al. / Psychiatry Research ∎ (∎∎∎∎) ∎∎∎–∎∎∎
2
2.2. Study assessments During the first visit, all bipolar disorder patients were evaluated at the time of discharge. Hospital records of bipolar disorder patients were used to extract general data information, including subtypes of the diagnosis, using a selfdesigned form. Meanwhile, clinical episode characteristics and medications of all bipolar disorder patients were recorded. The patients were followed-up for 2 years, including any possible recurrence visit at the time of readmission. The study used a prospective design to investigate medication compliance, disease recurrence and the recovery of social function, through a telephone or a home-visit interview, which was natural and non-interventional. All medication decisions given to patients during the study period were determined only by the clinicians themselves. Medication adherence was measured by the medication possession ratio (MPR). The MPR was calculated as the number of days that psychotropic drugs were taken in relation to the total number of days in the follow-up period according to the reports of the family members and the medical records of the patients (Lage and Hassan, 2009). Patients were classified into three groups: full compliance (MPR greater than 0.80), partial compliance (MPR greater than 0.50– 0.80), and non-compliance (MPR less than or equal to 0.50) (Sajatovic et al., 2007). The assessment of recurrence was judged comprehensively through the reports of patients and family members, the evaluation of researchers, and inpatient records of recurrent admission, which was considered the clinical criteria for affective episode according to DSM-IV. The Clinical Global Impressions scale for use in bipolar illness (CGI-BP) was used to determine the recurrence of affective episodes. Definition of recurrence was defined a priori as CGI-BP mania score Z3 or CGI-BP depression score Z 3. At baseline and follow-up visit, vocational functioning was assessed by the Global Assessment of Functioning (GAF) scales and employment status was calculated as employed or unemployed. Employed was defined that bipolar disorder outpatients could return to their primary work or school competently. 2.3. Statistics All of the bipolar disorder patients were classified into two subtypes, according to the DSM-IV: bipolar I disorder or bipolar II disorder. Differences between the subtypes were statistically analyzed for medication compliance rate, recurrence rate, and rate of recovery of social function. The statistical analyses were performed by the Statistical Package for the Social Science software release 17.0 (SPSS). Continuous variables are given as means7 standard deviations, and categorical variables are given as percentage. The chisquare test was used for comparisons between categorical variables, for which the level of statistical significance was α ¼ 0.05. Logistic regression analysis, using the method of backward likelihood ratios, was performed to examine the degree to which different independent variables predicted the dependent variables of recurrence within 1 year and 2 years. The independent variables were gender; age of onset; course of disease; educational level; marital status; character before disease; family history; previously hospitalized; frequency of hospitalizations; type of first episode; duration of definite diagnosis; diagnostic classification type; medication type; medication compliance; lack of family support; and no return to work. The level of significance for the logistic analyses was α ¼ 0.10.
3. Results 3.1. Baseline characteristics of patients A total of 252 patients with bipolar disorder were enrolled (44.8% were male; mean age¼ 38.27 13.5 S.D.). 132 patients (52.4%) were previously unemployed prior to hospitalization. At baseline, the GAF score was 70.478.6 S.D. and the medication type was 2.9 70.8 S.D. Of the 252 patients, 232 patients (92.1%) used atypical antipsychotics, 247 patients (98.0%) used mood stabilizers. Complete information was obtained for 210 of the patients (83.3%) from the 2-year follow-up, including 170 cases of bipolar I disorder and 40 cases of bipolar II disorder (see Table 1). 3.2. Follow-up comparisons of bipolar I and bipolar II patients Overall, the 1-year full-compliance rate was 41.0% and the 2year rate was 35.7%. Of the 210 patients, 89 patients (42.4%) experienced 116 episodes of recurrence within the 1-year observation period: 83 episodes with mania, 24 with depression, and nine mixed episodes. The mean time to recurrence was 5.9 73.6
months. Some 128 patients (61.0%) experienced 180 episodes of recurrence within the 2-year observation period: 126 episodes with mania, 40 with depression, and 14 with mixed episodes. The mean time to recurrence was 10.0 76.7 months. In all, 42.4% of patients recovered sufficiently to return to work or study within 1 year. Significant differences were found between the subtypes for the 1-year full-compliance rate (χ2 ¼4.032), the 1-year noncompliance rate (χ2 ¼3.927), the 2-year recurrence rate (χ2 ¼ 7.069) and the 2-year readmission rate (χ2 ¼5.288) (po0.05) (see Table 2). 3.3. Recurrence analysis The logistic regression (at the level of α ¼0.10) revealed four key findings (see Table 3). First, previous hospitalization, lack of family support, no return to work and medication type were risk factors for recurrence of bipolar disorder within 1 year of hospital Table 1 Sociodemographics, clinical episode characteristics and medications of all bipolar disorder patients and patients with complete information at baseline. Variable
Sociodemographics Gender, N (%) Male Female Age in years, mean 7 S.D. Positive family history, N (%) Character before disease, N (%) Introverted Extroverted Middle Clinical episode characteristics Course of disease, year Age of onset, year Duration of definite diagnosis, year Frequency of hospitalization Type of first episode, N (%) Manic Depressive Mixed Current episode, N (%) Manic Depressive Mixed Diagnostic classification types, N (%) Bipolar I Bipolar II Presence of psychotic symptoms, N (%) Employment status Employed Unemployed CGI-BP, mean7 S.D. GAF, mean7 S.D. Medicationsa Medication type, mean7 S.D. Atypical antipsychotics, N (%) Risperidone Olanzapine Quetiapine Typical antipsychotics, N (%) Mood stabilizers, N (%) Lithium Valproate Oxcarbazepine Lamotrigine Antidepressants, N (%) Benzodiazepines, N (%)
All patients Patients with (N ¼ 252) complete information (N ¼ 210)
113 (44.8) 139 (55.2) 38.2 713.5 64 (25.4)
85 (40.5) 125 (59.5) 39.4 713.4 52 (24.8)
121 (48.0) 84 (33.3) 47 (18.7)
97 (46.2) 69 (32.8) 44 (21.0)
10.8 7 10.5 27.4 710.4 8.5 79.6 3.17 3.5
11.6 710.6 27.8 7 10.4 9.0 79.7 3.5 73.7
123 (48.8) 128 (50.8) 1 (0.4)
100 (47.6) 109 (51.9) 1 (0.5)
180 (71.4) 53 (21.0) 19 (7.6)
151 (71.9) 44 (21.0) 15 (7.1)
204 (81.0) 48 (19.0) 104 (41.3)
170 (81.0) 40 (19.0) 88 (41.9)
120 (47.6) 132 (52.4)
98 (46.7) 112 (53.3)
1.7 7 0.6 70.4 7 8.6
1.8 7 0.5 72.5 7 9.3
2.9 70.8 232 (92.1) 111 (44.0) 58 (23.0) 30 (11.9) 7 (2.8) 247 (98.0) 153 (60.7) 140 (55.6) 18 (7.1) 19 (7.5) 29 (11.5) 102 (40.5)
2.9 70.8 195 (92.9) 93 (44.3) 47 (22.4) 24 (11.4) 4 (1.9) 207 (98.6) 126 (60.0) 122 (58.1) 18 (8.6) 15 (7.1) 23 (11.0) 86 (41.0)
CGI-BP: Clinical Global Impression scale for use in bipolar illness, GAF: Global Assessment of Functioning. a
Patients may have received more than 1 mediation type.
Please cite this article as: Li, C., et al., A 2-year follow-up study of discharged psychiatric patients with bipolar disorder. Psychiatry Research (2014), http://dx.doi.org/10.1016/j.psychres.2014.04.029i
C. Li et al. / Psychiatry Research ∎ (∎∎∎∎) ∎∎∎–∎∎∎
discharge. Second, medication compliance was a protective factor for recurrence within 1 year of hospital discharge. Third, medication type and being single were risk factors for recurrence within 2 years of hospital discharge. Fourth, medication compliance, being female, subtype bipolar II, and having a secondary school degree or higher were protective factors for recurrence within 2 years of hospital discharge.
4. Discussion In spite of significant advances in mediations, bipolar disorder, which was once thought to have a relatively favorable prognosis, remains a serious disability with a wide range of poor outcomes. Only one-third of bipolar disorder patients achieve full social and occupational functional recovery to their own pre-morbid levels (Huxley and Baldessarini, 2007). Yatham et al (2009) found that 46.7% of patients with bipolar disorder lived without a mood episode within 12 months of follow-up, after their first manic Table 2 Comparison of follow-up situations of discharged patients with bipolar disorder I and II subtypes. BP Iþ BP II BP I BP II χ2 (N ¼210, %) (N¼ 170, %) (N ¼ 40, %)
p Valuea
Compliance in 1 year Full Partial Non-compliance
86 (41.0) 60 (28.6) 64 (30.5)
64 (37.7) 49 (28.8) 57 (33.5)
22 (55.0) 11 (27.5) 7 (17.5)
4.032 0.045a 0.028 0.868 3.927 0.048a
Compliance in 2 years Full Partial Non-compliance
75 (35.7) 55 (26.2) 80 (38.1)
56 (32.9) 46 (27.1) 68 (40.0)
19 (47.5) 9 (22.5) 12 (30.0)
2.989 0.084 0.348 0.555 1.373 0.241
Recurrence in 1 year Recurrence Stable Readmission in 1 year
89 (42.4) 121 (57.6) 81 (38.6)
76 (44.7) 94 (55.3) 70 (41.2)
13 (32.5) 27 (67.5) 11 (27.5)
1.976 0.160
Recurrence in 2 years Recurrence 128 (61.0) Stable 82 (39.0) Readmission in 2 years 113 (53.8)
111 (65.3) 59 (34.7) 98 (57.6)
17 (42.5) 23 (57.5) 15 (37.5)
7.069 0.008a
Employment status Employed Unemployed
71 (41.8) 99 (58.2)
18 (45.0) 22 (55.0)
a
89 (42.4) 121 (57.6)
2.556 0.110
5.288 0.021a 0.139 0.709
Values are statistically significant.
Table 3 Independent variables associated with recurrence within 1 and 2 years after discharge from hospital in logistic regression analysis (α ¼ 0.10). Variable
Wald
Sig.
Exp (B)
95% CI for exp (B)
Recurrence within 1 year (N ¼ 210) Previously hospitalized 3.110 Medication type 6.021 Medication compliance 33.040 No return to work 3.931 Lack of family support 3.417 Constant 3.286
0.078 0.014 0.000 0.047 0.065 0.070
1.862 1.696 0.299 1.937 1.521 0.105
0.933–3.716 1.112–2.586 0.198–0.451 1.008–3.725 0.975–2.373
Recurrence within 2 years (N ¼ 210) Female 4.304 Bipolar II 3.437 Medication type 6.575 Educational level 3.960 Single marital status 3.538 Medication compliance 24.627 Constant 5.469
0.038 0.064 0.010 0.047 0.060 0.000 0.019
0.485 0.458 1.781 0.592 1.894 0.367 24.153
0.245–0.961 0.201–1.046 1.146–2.769 0.353–0.992 0.974–3.683 0.247–0.545
3
episode. The mean time-to-mood event was 7.9 months, according to survival analysis results. Kora et al (2008) reported that the 1-year recurrence rate was 35.7% among 584 patients followed up for 12 months, and their mean time to recurrence was 159.0 795.5 days. In our study, we found that the 1-year and 2-year recurrence rates were 42.4% and 61.0% respectively. The 1-year mean time to recurrence was 5.9 73.6 months and the 2-year mean time to recurrence was 10.0 7 6.7 months. Thus, the recurrence rates and the mean time to recurrence observed in the current study are similar to the results of previous studies, which indicate that the likelihood of recovery from bipolar disorder is not optimistic. During the period of maintenance treatment, the aim of medication for bipolar disorder patients should be to enhance and stabilize the patient's quality of life. However, the most serious obstacle to the effective treatment of bipolar disorder is non-adherence with medication (Jackson, 2008). Sajatovic et al (2008) summarized findings that indicated the range of medication non-adherence in bipolar disorder patients in different studies varies from 20% to 70%. Research has found that nonadherent patients, compared with adherent patients, have more prior suicide attempts (Sajatovic et al., 2008), poorer long-term clinical outcomes (Hong et al., 2011), and poorer quality of life (Crowe et al., 2011). They also have higher risk of recurrence and higher inpatient costs (Hong et al., 2011). The present study found that the 1-year and 2-year non-compliance rates of discharged patients with bipolar disorder were 30.5%, and 38.1%, respectively, which agrees with other results reported in the literature. This study found that patients with bipolar I and II had obvious differences during the follow-up period, including better medication adherence and lower recurrence rates among bipolar II patients. Logistic regression revealed that having bipolar II was a protective factor for recurrence within 2 years of hospital discharge, which was inconsistent with the view of Akiskal et al (2000) that most hypomanias in bipolar II pursue a recurrent course. Possible explanations for this are that bipolar II patients had the leading phase of depression, more complete insight, more anxiety and suicide, or more attention from their families, which may lead to higher medication compliance and, therefore, lower recurrence rates. Altman et al (2006) found several predictors of bipolar relapse based on their review of 38 studies. The predictors included a higher number of previous episodes, shorter intervals between episodes, and the persistence of affective symptoms and episodes. They also identified factors related to longer survival times, including psychotherapy, social support, and medication compliance. A study by de Dios et al. (2012) found that patients with bipolar disorder who had more previous affective episodes had an increased affective recurrence risk, and that being unemployed was associated with a shorter time to recurrence in Cox regression analysis. We found that patients who were hospitalized previously, lacked family support, or did not return to work were at a higher risk for recurrence of bipolar disorder, whereas medication compliance was a protective factor for recurrence. These findings are consistent with previously reported results. We also found that having a secondary school or higher education was a protective factor for recurrence within 2 years after being discharged from the hospital. A possible explanation for this may be that the patients with more education have better insight about the need for medication, which might reduce the chance of recurrence. This perspective is similar to the views of Yen et al. (2008) and Latalova (2012), who believe that better insight into treatment by bipolar patients can improve their poor clinical prognosis. The results of the current study show that strengthening medication adherence can prevent or reduce relapse and, therefore, help to improve the prognosis of patients with bipolar disorder, which is similar to the opinion expressed by Crowe
Please cite this article as: Li, C., et al., A 2-year follow-up study of discharged psychiatric patients with bipolar disorder. Psychiatry Research (2014), http://dx.doi.org/10.1016/j.psychres.2014.04.029i
C. Li et al. / Psychiatry Research ∎ (∎∎∎∎) ∎∎∎–∎∎∎
4
et al. (2011) and Gutiérrez-Rojas et al. (2010). To enhance the medication adherence of patients with bipolar disorder, we should address each of the four factors that influence adherence: patient, illness, medication and environmental (Crowe et al., 2011). This includes providing psycho-education (Berk et al., 2010), teaching patients to manage their illness by identifying prodromal signs of relapse (Swann, 2010), and reinforcing the patient-provider relationship (Zeber et al., 2008). Further prospective studies should be conducted on medication compliance in the future. 5. Conclusions Follow-up of patients with bipolar disorder after hospital discharge indicates that their situation is not optimistic; they have high recurrence rates, high non-compliance rates, and low recovery rates. Therefore, clinicians and social workers should pay more attention to hospital treatment, discharge planning and community rehabilitation. It is essential to reduce the variety of medications, strengthen family support, improve medication adherence, and encourage return to work as soon as possible, to prevent or reduce the recurrence of bipolar disorder. The primary limitations of the study were exclusion of outpatients and a relatively small sample size. It is also possible that some information could be biased because of the way in which follow-up interviews were conducted, because most of them were telephone interviews. Acknowledgments This project was supported by the Medical Scientific Research Fund of the Foshan Science and Technology Bureau (No.: 201208244) and Shunde WuZhongpei Memorial Hospital (No.:201201), Guangdong, China. We thank Professor Guodong Miao (from Department of Mood Disorders, Guangzhou Psychiatric Hospital, Guangdong, China) for his great clinical supervision. Appendix A. Supplementary material Supplementary data associated with this article can be found in the online version at http://dx.doi.org/10.1016/j.psychres.2014.04.029. References Akiskal, H.S., Bourgeois, M.L., Angst, J., Post, R., Moller, H., Hirschfeld, R., 2000. Reevaluating the prevalence of and diagnostic composition within the broad clinical spectrum of bipolar disorders. Journal of Affective Disorders 59 (Suppl. 1), S5–S30. Altman, S., Haeri, S., Cohen, L.J., Ten, A., Barron, E., Galynker, I.I., Duhamel, K.N., 2006. Predictors of relapse in bipolar disorder: a review. Journal of Psychiatric Practice 12, 269–282. Berk, L., Hallam, K.T., Colom, F., Vieta, E., Hasty, M., Macneil, C., Berk, M., 2010. Enhancing medication adherence in patients with bipolar disorder. Human Psychopharmacology 25, 1–16. Bobo, W.V., Shelton, R.C., 2010. Risperidone long-acting injectable for maintenance treatment in patients with bipolar disorder. Expert Review of Neurotherapeutics 10, 1637–1658. Crowe, M., Wilson, L., Inder, M., 2011. Patients' reports of the factors influencing medication adherence in bipolar disorder – an integrative review of the literature. International Journal of Nursing Studies 48, 894–903.
Cullen-Drill, M., Cullen-Dolce, D., 2008. Early and accurate diagnosis of bipolar II disorder leads to successful outcomes. Perspectives in Psychiatric Care 44, 110–119. de Dios, C., González-Pinto, A., Montes, J.M., Goikolea, J.M., Saiz-Ruiz, J., Prieto, E., Vieta, E., 2012. Predictors of recurrence in bipolar disorders in Spain (PREBIS study data). Journal of Affective Disorders 141, 406–414. Depp, C.A., Moore, D.J., Patterson, T.L., Lebowitz, B.D., Jeste, D.V., 2008. Psychosocial interventions and medication adherence in bipolar disorder. Dialogues in Clinical Neuroscience 10, 239–250. El-Mallakh, R.S., Elmaadawi, A.Z., Loganathan, M., Lohano, K., Gao, Y., 2010. Bipolar disorder: an update. Postgraduate Medicine 122, 24–31. Gutiérrez-Rojas, L., Jurado, D., Martínez-Ortega, J.M., Gurpegui, M., 2010. Poor adherence to treatment associated with a high recurrence in a bipolar disorder outpatient sample. Journal of Affective Disorders 127, 77–83. Hong, J., Reed, C., Novick, D., Haro, J.M., Aguado, J., 2011. Clinical and economic consequences of medication non-adherence in the treatment of patients with a manic/mixed episode of bipolar disorder: results from the European mania in bipolar longitudinal evaluation of medication (EMBLEM) study. Psychiatry Research 190, 110–114. Huxley, N., Baldessarini, R.J., 2007. Disability and its treatment in bipolar disorder patients. Bipolar Disorders 9, 183–196. Jackson, W.C., 2008. The importance of facilitating adherence in maintenance therapy for bipolar disorder. Journal of Clinical Psychiatry 69, e3. Kora, K., Saylan, M., Akkaya, C., Karamustafalioglu, N., Tomruk, N., Yasan, A., Oral, T., 2008. Predictive factors for time to remission and recurrence in patients treated for acute mania: health outcomes of manic episodes (HOME) study. The Primary Care Companion to the Journal of Clinical Psychiatry 10, 114–119. Kupka, R.W., Regeer, E.J., 2007. Bipolar mood disorders. Nederlands Tijdschrift voor Geneeskunde 151, 2256–2260. Lage, M.J., Hassan, M.K., 2009. The relationship between antipsychotic medication adherence and patient outcomes among individuals diagnosed with bipolar disorder: a retrospective study. Annals of General Psychiatry 8, 7. Latalova, K., 2012. Insight in bipolar disorder. Psychiatric Quarterly 83, 293–310. Leboyer, M., Kupfer, D.J., 2010. Bipolar disorder: new perspectives in health care and prevention. Journal of Clinical Psychiatry 71, 1689–1695. Lin, D., Mok, H., Yatham, L.N., 2006. Polytherapy in bipolar disorder. CNS Drugs 20, 29–42. Malhi, G.S., Adams, D., Cahill, C.M., Dodd, S., Berk, M., 2009. The management of individuals with bipolar disorder: a review of the evidence and its integration into clinical practice. Drugs 69, 2063–2101. Prasko, J., Ociskova, M., Kamaradova, D., Sedlackova, Z., Cerna, M., Mainerova, B., Sandoval, A., 2013. Bipolar affective disorder and psychoeducation. Neuroendocrinology Letters 34, 83–96. Price, A.L., Marzani-Nissen, G.R., 2012. Bipolar disorders: a review. American Family Physician 85, 483–493. Sajatovic, M., Bauer, M.S., Kilbourne, A.M., Vertrees, J.E., Williford, W., 2006. Selfreported medication treatment adherence among veterans with bipolar disorder. Psychiatric Services 57, 56–62. Sajatovic, M., Biswas, K., Kilbourne, A.K., Fenn, H., Williford, W., Bauer, M.S., 2008. Factors associated with prospective long-term treatment adherence among individuals with bipolar disorder. Psychiatric Services 59, 753–759. Sajatovic, M., Valenstein, M., Blow, F., Ganoczy, D., Ignacio, R., 2007. Treatment adherence with lithium and anticonvulsant medications among patients with bipolar disorder. Psychiatric Services 58, 855–863. Sienaert, P., de Fruyt, J., 2008. Psychoeducation in the treatment of bipolar disorder. Tijdschrift voor Psychiatrie 50, 509–518. Swann, A.C., 2010. Approaches to preventing relapse in bipolar disorder: addressing nonadherence and prodromal symptoms. Journal of Clinical Psychiatry 71, e35. Thase, ME., 2008. Maintenance therapy for bipolar disorder. Journal of Clinical Psychiatry 69, e32. Treuer, T., Tohen, M., 2010. Predicting the course and outcome of bipolar disorder: a review. European Psychiatry 25, 328–333. Yatham, L.N., Kauer-Sant'Anna, M., Bond, D.J., Lam, R.W., Torres, I., 2009. Course and outcome after the first manic episode in patients with bipolar disorder: prospective 12-month data from the systematic treatment optimization program for early mania project. Canadian Journal of Psychiatry 54, 105–112. Yen, C.F., Chen, C.S., Yen, J.Y., Ko, C.H., 2008. The predictive effect of insight on adverse clinical outcomes in bipolar I disorder: a two-year prospective study. Journal of Affective Disorders 108, 121–127. Zeber, J.E., Copeland, L.A., Good, C.B., Fine, M.J., Bauer, M.S., Kilbourne, A.M., 2008. Therapeutic alliance perceptions and medication adherence in patients with bipolar disorder. Journal of Affective Disorders 107, 53–62.
Please cite this article as: Li, C., et al., A 2-year follow-up study of discharged psychiatric patients with bipolar disorder. Psychiatry Research (2014), http://dx.doi.org/10.1016/j.psychres.2014.04.029i
Contents lists available at ScienceDirect
Psychiatry Research journal homepage: www.elsevier.com/locate/psychres
A 2-year follow-up study of discharged psychiatric patients with bipolar disorder Chunyang Li, Chao Chen n, Bin Qiu, Guang Yang Department of Psychiatry, WuZhongpei Memorial Hospital, No. 3 Jianmin Road, Daliang Town, Shunde District of Foshan City, Guangdong 528300, China
art ic l e i nf o
a b s t r a c t
Article history: Received 24 January 2014 Received in revised form 31 March 2014 Accepted 9 April 2014
This study investigated medication compliance, disease recurrence and the recovery of social function in discharged psychiatric patients with bipolar disorder. A 2-year follow-up was conducted on all patients with bipolar disorder, who were hospitalized in our psychiatric department between June 2010 and May 2011. Risk factors for recurrence were analyzed based on a self-designed questionnaire. Of the 252 patients in the study, 210 had complete information (83.3%) for the 2-year follow-up: 170 cases of bipolar I disorder and 40 cases of bipolar II disorder. The 1-year and 2-year full-compliance rates were 41.0% and 35.7%, respectively. The 1-year and 2-year recurrence rates were 42.4% and 61.0%, respectively. Statistically significant differences in rates were found between the bipolar subtypes for 1-year full compliance, 1-year non-compliance, 2-year recurrence, and 2-year readmission. Logistic regression identified different sets of independent variables that were risk factors for recurrence, and protective factors for recurrence at 1 year and 2 years after hospital discharge. The results of the follow-up indicated that the situation of patients with bipolar disorder after discharge is not optimistic, because of high recurrence rates, high non-compliance rates and low recovery rates. Clinical and social experts should pay more attention to the situation. & 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Bipolar disorder Recurrence Medication compliance
1. Introduction Bipolar disorder is a common, disabling illness that is chronic and recurrent (Lin et al., 2006; Malhi et al., 2009; Leboyer and Kupfer, 2010). An early correct diagnosis of bipolar disorder, in conjunction with appropriate treatment, can contribute to an improved prognosis (Price and Marzani-Nissen, 2012; Cullen-Drill and Cullen-Dolce, 2008). Many recent studies have shown that pharmacotherapy and psychotherapy can help patients with bipolar disorder achieve remission and reduce relapse (Thase, 2008; Prasko et al., 2013). Although pharmacological and non-pharmacological treatments have made progress in treating bipolar disorder, the disorder often produces multiple relapses and impaired psychological functioning (Treuer and Tohen, 2010; Kupka and Regeer, 2007), and the overall prognosis of bipolar disorder does not appear to have been altered by such treatments (El-Mallakh et al., 2010). Medication non-adherence during the maintenance treatment of bipolar disorder is common, resulting in many adverse outcomes (Sajatovic et al., 2006; Bobo and Shelton, 2010). Given the correlation of non-adherence with high risk of relapse and hospitalization among bipolar disorder patients, it is important to improve medication
n
Corresponding author. Tel.: þ 86 757 2928 2895; fax: þ 86 757 2229 8820. E-mail address: [email protected] (C. Chen).
adherence for effective treatment (Depp et al., 2008). Many studies have shown that providing psycho-education to patients with bipolar disorder can increase medication adherence and prevent relapse (Sienaert and de Fruyt, 2008). We conducted a 2-year, follow-up study to investigate the degree of medication adherence and the recovery status of bipolar disorder patients discharged from a psychiatric hospital. The study was intended to provide relevant information that would contribute to improve prognosis and prevent relapse of bipolar disorder. This article summarizes the results of that study.
2. Methods 2.1. Patients The study sample consisted of patients who (1) were hospitalized for some time between June 2010 and May 2011 in our psychiatric department, and (2) were diagnosed with bipolar disorder, according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), by one attending physician and one associate chief physician. Patients were enrolled in the 2-year follow-up study regardless of their sex, age or subtype of bipolar disorder. All patients or their legal representatives signed informed consent before the patients entered the study. The study was approved by the Ethics Committee of WuZhongpei Memorial Hospital, Shunde District of Foshan City.
http://dx.doi.org/10.1016/j.psychres.2014.04.029 0165-1781/& 2014 Elsevier Ireland Ltd. All rights reserved.
Please cite this article as: Li, C., et al., A 2-year follow-up study of discharged psychiatric patients with bipolar disorder. Psychiatry Research (2014), http://dx.doi.org/10.1016/j.psychres.2014.04.029i
C. Li et al. / Psychiatry Research ∎ (∎∎∎∎) ∎∎∎–∎∎∎
2
2.2. Study assessments During the first visit, all bipolar disorder patients were evaluated at the time of discharge. Hospital records of bipolar disorder patients were used to extract general data information, including subtypes of the diagnosis, using a selfdesigned form. Meanwhile, clinical episode characteristics and medications of all bipolar disorder patients were recorded. The patients were followed-up for 2 years, including any possible recurrence visit at the time of readmission. The study used a prospective design to investigate medication compliance, disease recurrence and the recovery of social function, through a telephone or a home-visit interview, which was natural and non-interventional. All medication decisions given to patients during the study period were determined only by the clinicians themselves. Medication adherence was measured by the medication possession ratio (MPR). The MPR was calculated as the number of days that psychotropic drugs were taken in relation to the total number of days in the follow-up period according to the reports of the family members and the medical records of the patients (Lage and Hassan, 2009). Patients were classified into three groups: full compliance (MPR greater than 0.80), partial compliance (MPR greater than 0.50– 0.80), and non-compliance (MPR less than or equal to 0.50) (Sajatovic et al., 2007). The assessment of recurrence was judged comprehensively through the reports of patients and family members, the evaluation of researchers, and inpatient records of recurrent admission, which was considered the clinical criteria for affective episode according to DSM-IV. The Clinical Global Impressions scale for use in bipolar illness (CGI-BP) was used to determine the recurrence of affective episodes. Definition of recurrence was defined a priori as CGI-BP mania score Z3 or CGI-BP depression score Z 3. At baseline and follow-up visit, vocational functioning was assessed by the Global Assessment of Functioning (GAF) scales and employment status was calculated as employed or unemployed. Employed was defined that bipolar disorder outpatients could return to their primary work or school competently. 2.3. Statistics All of the bipolar disorder patients were classified into two subtypes, according to the DSM-IV: bipolar I disorder or bipolar II disorder. Differences between the subtypes were statistically analyzed for medication compliance rate, recurrence rate, and rate of recovery of social function. The statistical analyses were performed by the Statistical Package for the Social Science software release 17.0 (SPSS). Continuous variables are given as means7 standard deviations, and categorical variables are given as percentage. The chisquare test was used for comparisons between categorical variables, for which the level of statistical significance was α ¼ 0.05. Logistic regression analysis, using the method of backward likelihood ratios, was performed to examine the degree to which different independent variables predicted the dependent variables of recurrence within 1 year and 2 years. The independent variables were gender; age of onset; course of disease; educational level; marital status; character before disease; family history; previously hospitalized; frequency of hospitalizations; type of first episode; duration of definite diagnosis; diagnostic classification type; medication type; medication compliance; lack of family support; and no return to work. The level of significance for the logistic analyses was α ¼ 0.10.
3. Results 3.1. Baseline characteristics of patients A total of 252 patients with bipolar disorder were enrolled (44.8% were male; mean age¼ 38.27 13.5 S.D.). 132 patients (52.4%) were previously unemployed prior to hospitalization. At baseline, the GAF score was 70.478.6 S.D. and the medication type was 2.9 70.8 S.D. Of the 252 patients, 232 patients (92.1%) used atypical antipsychotics, 247 patients (98.0%) used mood stabilizers. Complete information was obtained for 210 of the patients (83.3%) from the 2-year follow-up, including 170 cases of bipolar I disorder and 40 cases of bipolar II disorder (see Table 1). 3.2. Follow-up comparisons of bipolar I and bipolar II patients Overall, the 1-year full-compliance rate was 41.0% and the 2year rate was 35.7%. Of the 210 patients, 89 patients (42.4%) experienced 116 episodes of recurrence within the 1-year observation period: 83 episodes with mania, 24 with depression, and nine mixed episodes. The mean time to recurrence was 5.9 73.6
months. Some 128 patients (61.0%) experienced 180 episodes of recurrence within the 2-year observation period: 126 episodes with mania, 40 with depression, and 14 with mixed episodes. The mean time to recurrence was 10.0 76.7 months. In all, 42.4% of patients recovered sufficiently to return to work or study within 1 year. Significant differences were found between the subtypes for the 1-year full-compliance rate (χ2 ¼4.032), the 1-year noncompliance rate (χ2 ¼3.927), the 2-year recurrence rate (χ2 ¼ 7.069) and the 2-year readmission rate (χ2 ¼5.288) (po0.05) (see Table 2). 3.3. Recurrence analysis The logistic regression (at the level of α ¼0.10) revealed four key findings (see Table 3). First, previous hospitalization, lack of family support, no return to work and medication type were risk factors for recurrence of bipolar disorder within 1 year of hospital Table 1 Sociodemographics, clinical episode characteristics and medications of all bipolar disorder patients and patients with complete information at baseline. Variable
Sociodemographics Gender, N (%) Male Female Age in years, mean 7 S.D. Positive family history, N (%) Character before disease, N (%) Introverted Extroverted Middle Clinical episode characteristics Course of disease, year Age of onset, year Duration of definite diagnosis, year Frequency of hospitalization Type of first episode, N (%) Manic Depressive Mixed Current episode, N (%) Manic Depressive Mixed Diagnostic classification types, N (%) Bipolar I Bipolar II Presence of psychotic symptoms, N (%) Employment status Employed Unemployed CGI-BP, mean7 S.D. GAF, mean7 S.D. Medicationsa Medication type, mean7 S.D. Atypical antipsychotics, N (%) Risperidone Olanzapine Quetiapine Typical antipsychotics, N (%) Mood stabilizers, N (%) Lithium Valproate Oxcarbazepine Lamotrigine Antidepressants, N (%) Benzodiazepines, N (%)
All patients Patients with (N ¼ 252) complete information (N ¼ 210)
113 (44.8) 139 (55.2) 38.2 713.5 64 (25.4)
85 (40.5) 125 (59.5) 39.4 713.4 52 (24.8)
121 (48.0) 84 (33.3) 47 (18.7)
97 (46.2) 69 (32.8) 44 (21.0)
10.8 7 10.5 27.4 710.4 8.5 79.6 3.17 3.5
11.6 710.6 27.8 7 10.4 9.0 79.7 3.5 73.7
123 (48.8) 128 (50.8) 1 (0.4)
100 (47.6) 109 (51.9) 1 (0.5)
180 (71.4) 53 (21.0) 19 (7.6)
151 (71.9) 44 (21.0) 15 (7.1)
204 (81.0) 48 (19.0) 104 (41.3)
170 (81.0) 40 (19.0) 88 (41.9)
120 (47.6) 132 (52.4)
98 (46.7) 112 (53.3)
1.7 7 0.6 70.4 7 8.6
1.8 7 0.5 72.5 7 9.3
2.9 70.8 232 (92.1) 111 (44.0) 58 (23.0) 30 (11.9) 7 (2.8) 247 (98.0) 153 (60.7) 140 (55.6) 18 (7.1) 19 (7.5) 29 (11.5) 102 (40.5)
2.9 70.8 195 (92.9) 93 (44.3) 47 (22.4) 24 (11.4) 4 (1.9) 207 (98.6) 126 (60.0) 122 (58.1) 18 (8.6) 15 (7.1) 23 (11.0) 86 (41.0)
CGI-BP: Clinical Global Impression scale for use in bipolar illness, GAF: Global Assessment of Functioning. a
Patients may have received more than 1 mediation type.
Please cite this article as: Li, C., et al., A 2-year follow-up study of discharged psychiatric patients with bipolar disorder. Psychiatry Research (2014), http://dx.doi.org/10.1016/j.psychres.2014.04.029i
C. Li et al. / Psychiatry Research ∎ (∎∎∎∎) ∎∎∎–∎∎∎
discharge. Second, medication compliance was a protective factor for recurrence within 1 year of hospital discharge. Third, medication type and being single were risk factors for recurrence within 2 years of hospital discharge. Fourth, medication compliance, being female, subtype bipolar II, and having a secondary school degree or higher were protective factors for recurrence within 2 years of hospital discharge.
4. Discussion In spite of significant advances in mediations, bipolar disorder, which was once thought to have a relatively favorable prognosis, remains a serious disability with a wide range of poor outcomes. Only one-third of bipolar disorder patients achieve full social and occupational functional recovery to their own pre-morbid levels (Huxley and Baldessarini, 2007). Yatham et al (2009) found that 46.7% of patients with bipolar disorder lived without a mood episode within 12 months of follow-up, after their first manic Table 2 Comparison of follow-up situations of discharged patients with bipolar disorder I and II subtypes. BP Iþ BP II BP I BP II χ2 (N ¼210, %) (N¼ 170, %) (N ¼ 40, %)
p Valuea
Compliance in 1 year Full Partial Non-compliance
86 (41.0) 60 (28.6) 64 (30.5)
64 (37.7) 49 (28.8) 57 (33.5)
22 (55.0) 11 (27.5) 7 (17.5)
4.032 0.045a 0.028 0.868 3.927 0.048a
Compliance in 2 years Full Partial Non-compliance
75 (35.7) 55 (26.2) 80 (38.1)
56 (32.9) 46 (27.1) 68 (40.0)
19 (47.5) 9 (22.5) 12 (30.0)
2.989 0.084 0.348 0.555 1.373 0.241
Recurrence in 1 year Recurrence Stable Readmission in 1 year
89 (42.4) 121 (57.6) 81 (38.6)
76 (44.7) 94 (55.3) 70 (41.2)
13 (32.5) 27 (67.5) 11 (27.5)
1.976 0.160
Recurrence in 2 years Recurrence 128 (61.0) Stable 82 (39.0) Readmission in 2 years 113 (53.8)
111 (65.3) 59 (34.7) 98 (57.6)
17 (42.5) 23 (57.5) 15 (37.5)
7.069 0.008a
Employment status Employed Unemployed
71 (41.8) 99 (58.2)
18 (45.0) 22 (55.0)
a
89 (42.4) 121 (57.6)
2.556 0.110
5.288 0.021a 0.139 0.709
Values are statistically significant.
Table 3 Independent variables associated with recurrence within 1 and 2 years after discharge from hospital in logistic regression analysis (α ¼ 0.10). Variable
Wald
Sig.
Exp (B)
95% CI for exp (B)
Recurrence within 1 year (N ¼ 210) Previously hospitalized 3.110 Medication type 6.021 Medication compliance 33.040 No return to work 3.931 Lack of family support 3.417 Constant 3.286
0.078 0.014 0.000 0.047 0.065 0.070
1.862 1.696 0.299 1.937 1.521 0.105
0.933–3.716 1.112–2.586 0.198–0.451 1.008–3.725 0.975–2.373
Recurrence within 2 years (N ¼ 210) Female 4.304 Bipolar II 3.437 Medication type 6.575 Educational level 3.960 Single marital status 3.538 Medication compliance 24.627 Constant 5.469
0.038 0.064 0.010 0.047 0.060 0.000 0.019
0.485 0.458 1.781 0.592 1.894 0.367 24.153
0.245–0.961 0.201–1.046 1.146–2.769 0.353–0.992 0.974–3.683 0.247–0.545
3
episode. The mean time-to-mood event was 7.9 months, according to survival analysis results. Kora et al (2008) reported that the 1-year recurrence rate was 35.7% among 584 patients followed up for 12 months, and their mean time to recurrence was 159.0 795.5 days. In our study, we found that the 1-year and 2-year recurrence rates were 42.4% and 61.0% respectively. The 1-year mean time to recurrence was 5.9 73.6 months and the 2-year mean time to recurrence was 10.0 7 6.7 months. Thus, the recurrence rates and the mean time to recurrence observed in the current study are similar to the results of previous studies, which indicate that the likelihood of recovery from bipolar disorder is not optimistic. During the period of maintenance treatment, the aim of medication for bipolar disorder patients should be to enhance and stabilize the patient's quality of life. However, the most serious obstacle to the effective treatment of bipolar disorder is non-adherence with medication (Jackson, 2008). Sajatovic et al (2008) summarized findings that indicated the range of medication non-adherence in bipolar disorder patients in different studies varies from 20% to 70%. Research has found that nonadherent patients, compared with adherent patients, have more prior suicide attempts (Sajatovic et al., 2008), poorer long-term clinical outcomes (Hong et al., 2011), and poorer quality of life (Crowe et al., 2011). They also have higher risk of recurrence and higher inpatient costs (Hong et al., 2011). The present study found that the 1-year and 2-year non-compliance rates of discharged patients with bipolar disorder were 30.5%, and 38.1%, respectively, which agrees with other results reported in the literature. This study found that patients with bipolar I and II had obvious differences during the follow-up period, including better medication adherence and lower recurrence rates among bipolar II patients. Logistic regression revealed that having bipolar II was a protective factor for recurrence within 2 years of hospital discharge, which was inconsistent with the view of Akiskal et al (2000) that most hypomanias in bipolar II pursue a recurrent course. Possible explanations for this are that bipolar II patients had the leading phase of depression, more complete insight, more anxiety and suicide, or more attention from their families, which may lead to higher medication compliance and, therefore, lower recurrence rates. Altman et al (2006) found several predictors of bipolar relapse based on their review of 38 studies. The predictors included a higher number of previous episodes, shorter intervals between episodes, and the persistence of affective symptoms and episodes. They also identified factors related to longer survival times, including psychotherapy, social support, and medication compliance. A study by de Dios et al. (2012) found that patients with bipolar disorder who had more previous affective episodes had an increased affective recurrence risk, and that being unemployed was associated with a shorter time to recurrence in Cox regression analysis. We found that patients who were hospitalized previously, lacked family support, or did not return to work were at a higher risk for recurrence of bipolar disorder, whereas medication compliance was a protective factor for recurrence. These findings are consistent with previously reported results. We also found that having a secondary school or higher education was a protective factor for recurrence within 2 years after being discharged from the hospital. A possible explanation for this may be that the patients with more education have better insight about the need for medication, which might reduce the chance of recurrence. This perspective is similar to the views of Yen et al. (2008) and Latalova (2012), who believe that better insight into treatment by bipolar patients can improve their poor clinical prognosis. The results of the current study show that strengthening medication adherence can prevent or reduce relapse and, therefore, help to improve the prognosis of patients with bipolar disorder, which is similar to the opinion expressed by Crowe
Please cite this article as: Li, C., et al., A 2-year follow-up study of discharged psychiatric patients with bipolar disorder. Psychiatry Research (2014), http://dx.doi.org/10.1016/j.psychres.2014.04.029i
C. Li et al. / Psychiatry Research ∎ (∎∎∎∎) ∎∎∎–∎∎∎
4
et al. (2011) and Gutiérrez-Rojas et al. (2010). To enhance the medication adherence of patients with bipolar disorder, we should address each of the four factors that influence adherence: patient, illness, medication and environmental (Crowe et al., 2011). This includes providing psycho-education (Berk et al., 2010), teaching patients to manage their illness by identifying prodromal signs of relapse (Swann, 2010), and reinforcing the patient-provider relationship (Zeber et al., 2008). Further prospective studies should be conducted on medication compliance in the future. 5. Conclusions Follow-up of patients with bipolar disorder after hospital discharge indicates that their situation is not optimistic; they have high recurrence rates, high non-compliance rates, and low recovery rates. Therefore, clinicians and social workers should pay more attention to hospital treatment, discharge planning and community rehabilitation. It is essential to reduce the variety of medications, strengthen family support, improve medication adherence, and encourage return to work as soon as possible, to prevent or reduce the recurrence of bipolar disorder. The primary limitations of the study were exclusion of outpatients and a relatively small sample size. It is also possible that some information could be biased because of the way in which follow-up interviews were conducted, because most of them were telephone interviews. Acknowledgments This project was supported by the Medical Scientific Research Fund of the Foshan Science and Technology Bureau (No.: 201208244) and Shunde WuZhongpei Memorial Hospital (No.:201201), Guangdong, China. We thank Professor Guodong Miao (from Department of Mood Disorders, Guangzhou Psychiatric Hospital, Guangdong, China) for his great clinical supervision. Appendix A. Supplementary material Supplementary data associated with this article can be found in the online version at http://dx.doi.org/10.1016/j.psychres.2014.04.029. References Akiskal, H.S., Bourgeois, M.L., Angst, J., Post, R., Moller, H., Hirschfeld, R., 2000. Reevaluating the prevalence of and diagnostic composition within the broad clinical spectrum of bipolar disorders. Journal of Affective Disorders 59 (Suppl. 1), S5–S30. Altman, S., Haeri, S., Cohen, L.J., Ten, A., Barron, E., Galynker, I.I., Duhamel, K.N., 2006. Predictors of relapse in bipolar disorder: a review. Journal of Psychiatric Practice 12, 269–282. Berk, L., Hallam, K.T., Colom, F., Vieta, E., Hasty, M., Macneil, C., Berk, M., 2010. Enhancing medication adherence in patients with bipolar disorder. Human Psychopharmacology 25, 1–16. Bobo, W.V., Shelton, R.C., 2010. Risperidone long-acting injectable for maintenance treatment in patients with bipolar disorder. Expert Review of Neurotherapeutics 10, 1637–1658. Crowe, M., Wilson, L., Inder, M., 2011. Patients' reports of the factors influencing medication adherence in bipolar disorder – an integrative review of the literature. International Journal of Nursing Studies 48, 894–903.
Cullen-Drill, M., Cullen-Dolce, D., 2008. Early and accurate diagnosis of bipolar II disorder leads to successful outcomes. Perspectives in Psychiatric Care 44, 110–119. de Dios, C., González-Pinto, A., Montes, J.M., Goikolea, J.M., Saiz-Ruiz, J., Prieto, E., Vieta, E., 2012. Predictors of recurrence in bipolar disorders in Spain (PREBIS study data). Journal of Affective Disorders 141, 406–414. Depp, C.A., Moore, D.J., Patterson, T.L., Lebowitz, B.D., Jeste, D.V., 2008. Psychosocial interventions and medication adherence in bipolar disorder. Dialogues in Clinical Neuroscience 10, 239–250. El-Mallakh, R.S., Elmaadawi, A.Z., Loganathan, M., Lohano, K., Gao, Y., 2010. Bipolar disorder: an update. Postgraduate Medicine 122, 24–31. Gutiérrez-Rojas, L., Jurado, D., Martínez-Ortega, J.M., Gurpegui, M., 2010. Poor adherence to treatment associated with a high recurrence in a bipolar disorder outpatient sample. Journal of Affective Disorders 127, 77–83. Hong, J., Reed, C., Novick, D., Haro, J.M., Aguado, J., 2011. Clinical and economic consequences of medication non-adherence in the treatment of patients with a manic/mixed episode of bipolar disorder: results from the European mania in bipolar longitudinal evaluation of medication (EMBLEM) study. Psychiatry Research 190, 110–114. Huxley, N., Baldessarini, R.J., 2007. Disability and its treatment in bipolar disorder patients. Bipolar Disorders 9, 183–196. Jackson, W.C., 2008. The importance of facilitating adherence in maintenance therapy for bipolar disorder. Journal of Clinical Psychiatry 69, e3. Kora, K., Saylan, M., Akkaya, C., Karamustafalioglu, N., Tomruk, N., Yasan, A., Oral, T., 2008. Predictive factors for time to remission and recurrence in patients treated for acute mania: health outcomes of manic episodes (HOME) study. The Primary Care Companion to the Journal of Clinical Psychiatry 10, 114–119. Kupka, R.W., Regeer, E.J., 2007. Bipolar mood disorders. Nederlands Tijdschrift voor Geneeskunde 151, 2256–2260. Lage, M.J., Hassan, M.K., 2009. The relationship between antipsychotic medication adherence and patient outcomes among individuals diagnosed with bipolar disorder: a retrospective study. Annals of General Psychiatry 8, 7. Latalova, K., 2012. Insight in bipolar disorder. Psychiatric Quarterly 83, 293–310. Leboyer, M., Kupfer, D.J., 2010. Bipolar disorder: new perspectives in health care and prevention. Journal of Clinical Psychiatry 71, 1689–1695. Lin, D., Mok, H., Yatham, L.N., 2006. Polytherapy in bipolar disorder. CNS Drugs 20, 29–42. Malhi, G.S., Adams, D., Cahill, C.M., Dodd, S., Berk, M., 2009. The management of individuals with bipolar disorder: a review of the evidence and its integration into clinical practice. Drugs 69, 2063–2101. Prasko, J., Ociskova, M., Kamaradova, D., Sedlackova, Z., Cerna, M., Mainerova, B., Sandoval, A., 2013. Bipolar affective disorder and psychoeducation. Neuroendocrinology Letters 34, 83–96. Price, A.L., Marzani-Nissen, G.R., 2012. Bipolar disorders: a review. American Family Physician 85, 483–493. Sajatovic, M., Bauer, M.S., Kilbourne, A.M., Vertrees, J.E., Williford, W., 2006. Selfreported medication treatment adherence among veterans with bipolar disorder. Psychiatric Services 57, 56–62. Sajatovic, M., Biswas, K., Kilbourne, A.K., Fenn, H., Williford, W., Bauer, M.S., 2008. Factors associated with prospective long-term treatment adherence among individuals with bipolar disorder. Psychiatric Services 59, 753–759. Sajatovic, M., Valenstein, M., Blow, F., Ganoczy, D., Ignacio, R., 2007. Treatment adherence with lithium and anticonvulsant medications among patients with bipolar disorder. Psychiatric Services 58, 855–863. Sienaert, P., de Fruyt, J., 2008. Psychoeducation in the treatment of bipolar disorder. Tijdschrift voor Psychiatrie 50, 509–518. Swann, A.C., 2010. Approaches to preventing relapse in bipolar disorder: addressing nonadherence and prodromal symptoms. Journal of Clinical Psychiatry 71, e35. Thase, ME., 2008. Maintenance therapy for bipolar disorder. Journal of Clinical Psychiatry 69, e32. Treuer, T., Tohen, M., 2010. Predicting the course and outcome of bipolar disorder: a review. European Psychiatry 25, 328–333. Yatham, L.N., Kauer-Sant'Anna, M., Bond, D.J., Lam, R.W., Torres, I., 2009. Course and outcome after the first manic episode in patients with bipolar disorder: prospective 12-month data from the systematic treatment optimization program for early mania project. Canadian Journal of Psychiatry 54, 105–112. Yen, C.F., Chen, C.S., Yen, J.Y., Ko, C.H., 2008. The predictive effect of insight on adverse clinical outcomes in bipolar I disorder: a two-year prospective study. Journal of Affective Disorders 108, 121–127. Zeber, J.E., Copeland, L.A., Good, C.B., Fine, M.J., Bauer, M.S., Kilbourne, A.M., 2008. Therapeutic alliance perceptions and medication adherence in patients with bipolar disorder. Journal of Affective Disorders 107, 53–62.
Please cite this article as: Li, C., et al., A 2-year follow-up study of discharged psychiatric patients with bipolar disorder. Psychiatry Research (2014), http://dx.doi.org/10.1016/j.psychres.2014.04.029i
