Use of Treatment Services in a Comparative Effectiveness Study of Bipolar Disorder

Participants in the two treatment groups (Li+OPT versus OPT only) did not significantly differ in the total number of services used in either 12-week period. There were also no significant associations between treatment group and use of medical services or counseling services. At week 12, the mean±SD number of total services reported to be used in the prior three months was 5.40±10.00. The 246 participants used 1.07±2.17 medical services and 1.98±6.03 counseling services. At week 24 (N=236), they reported using 5.90±11.20 total services, 1.31±3.23 medical services, and 1.81±4.98 counseling services. The distribution of total services was positively skewed, with over 80% of participants (N=189) recording between zero and ten service visits (range=0–93). Number of medical services and number of counseling services were also positively skewed but had lower counts than total number of services. This was expected because we counted only a subset of total services.

We found that outpatients with higher depressive symptoms (on the MADRS) and manic symptoms (on the YMRS) had higher rates of using medical services (Table 1). Specifically, ten-unit increases in MADRS score and YMRS score resulted in a 20% and 48% increase, respectively, in rate of using medical services. MADRS, YMRS, and CGI-BP-S scores were marginally associated with total number of services (p<.06). Therefore, a ten-unit increase on the MADRS and YMRS resulted in 14% and 25% higher rates, respectively, of using all services. A one-unit increase on the CGI-BP-S resulted in a 13% higher rate of using medical services. Adjusting for visit, analyses indicated that both side-effect intensity and side-effect interference (FISER) were associated with the use of all services such that a one-unit increase in side-effect intensity and interference resulted in an 11% and 17% increased rate, respectively, of using all services (p<.01), but frequency of side effects was not associated with use of treatment services.

Participants with psychiatric conditions comorbid with bipolar disorder had higher rates of using all types of treatment services as well as medical and counseling services specifically (all p<.05) (Table 1). Each additional psychiatric comorbidity resulted in a 25% higher rate of using all services, a 35% higher rate of using counseling services, and an 11% higher rate of using medical services. Those who had an anxiety disorder (posttraumatic stress disorder, panic disorder, agoraphobia, obsessive-compulsive disorder, generalized anxiety disorder, social phobia, or a specific phobia) had a 25% higher rate of using all types of treatment services (Table 1). Given the association of anxiety disorders and use of services, we conducted follow-up analyses to examine specific anxiety disorders. We found a strong association between using more treatment services and having obsessive-compulsive disorder (IRR=2.21, p<.01) but not panic, phobia, generalized anxiety disorder, or posttraumatic stress disorder.

In regard to medical comorbidities, participants with high (exceeding 100 mg/dl) versus normal fasting plasma glucose used more than twice as many medical services but nearly half (46%) as many counseling services (Table 1).

Each multivariate model included an effect for time, forced into the model during variable selection, and considered the entry of all covariates in Table 1. The effects in the multivariate analysis were adjusted for all other covariates that entered the model. Analyses showed that number of psychiatric comorbidities (IRR=1.29, p=.003), obesity (IRR=.63, p=.03), and side-effect interference (IRR=1.19, p=.02) independently predicted use of all services. High glucose (IRR=2.25, p=.002) independently predicted use of medical services, and manic symptoms marginally predicted use of medical services (IRR=1.04, p=.07). High glucose (IRR=.53, p=.05) and side-effect interference (IRR=1.21, p=.02) predicted use of counseling services.

Participants who were older (middle age) (IRR=1.02, p=.01), had lived in the United States longer (IRR=1.02, p=.01), and were unemployed (IRR=1.84, p=.01) had higher rates of using all services, whereas use of psychotherapy was not significantly associated with any demographic or clinical variable (Tables 2 and 3).

In regard to the attrition analyses, we found that the dropout group had a higher proportion of men (p=.04), single or never-married individuals (p=.04), unemployed individuals (p=.04), and diagnosis of a substance use disorder (p=.02).

Individuals with bipolar disorder experience a substantial burden of medical and psychiatric comorbidity, yet reports of how they use treatment services have been inconsistent (2–5,7,8). This study contributes to the limited but emerging literature on service utilization in a relatively representative population of outpatients with bipolar disorder. Neither randomization to low or moderate doses of lithium compared with no lithium nor progression from week 12 to week 24 of the study appeared to affect service utilization, but we found several predictors of differential service use among outpatients with bipolar disorder. This study furthers our understanding of health behavior (personal health practices and use of health services), a key component of understanding health service use and improving outcomes, including perceived and evaluated health status and consumer satisfaction (29).

Current psychological symptoms of bipolar disorder were associated with increased utilization of medical services, but not counseling services. Furthermore, compared with depressive symptoms, manic symptoms were more strongly associated with service utilization. Thus it seems that a more severe course of mental illness (particularly mania) may encourage seeking treatment for general physical but not psychological problems. Of note, only the association with mania persisted when the multivariate analyses were conducted, suggesting that several of the variables (depression and anxiety, for example) were collinear or did not independently have strong effects on service utilization (Table 1).

Participants who rated their side effects as more intense, frequent, and burdensome tended to seek not only medical services but also counseling and more overall services than sought by other participants—a finding that persisted in the multivariate analyses. These data suggest that physical symptoms, as opposed to psychiatric and mood symptoms, may prompt individuals with bipolar disorder to seek counseling services. Physical symptoms may have less mutable characteristics (degree to which they can change service utilization), but they still have some degree of mutability, and this finding can inform clinicians about whom to target for services (such as individuals with high psychological distress) (29). These discrepant findings highlight the need for future research to assess the demographic and psychiatric correlates of seeking counseling services, particularly because other studies have found that individuals with bipolar disorder do not tend to seek counseling services (30,31).

We also found that among participants with bipolar disorder, characteristics with low to no degree of mutability generally predicted their likelihood to seek services and specifically predicted utilization among those who were of middle age, who lived in the United States longer compared with others, and who were unemployed. These findings suggest that individuals who are younger, recent immigrants, or unemployed may underutilize services and could benefit from close monitoring by providers when they do seek services. We also found that men, single or never-married participants, unemployed participants, and substance users tended to drop out of the study at greater rates than others, which may suggest that these individuals are at higher risk for not adequately using medical services.

Psychiatric comorbidities, particularly anxiety disorders, predicted higher rates of using all treatment services, further suggesting that individuals with more comorbid diagnoses have more insight into their need for help and thus seek more treatment services than individuals with just one diagnosis (15). Anxiety has been shown to increase concern for one’s health and report of somatic symptoms (32). High glucose levels predicted the use of medical and counseling services (also shown in the multivariate models). In the multivariate model, obesity predicted the use of all services but not counseling or medical services specifically. These latter findings are particularly notable because obesity is associated with low utilization of counseling services (33), which in turn may contribute to how this condition affects individuals’ overall health (34). The known health risks of obesity alone (35), compounded by the worsened outcomes seen among obese patients with bipolar disorder (36), highlight the importance of understanding the complex relationships between obesity and use of services because this will further our knowledge of both predisposing (demographic characteristics and comorbid diagnoses) and need (perceived and evaluated illness) factors of health utilization (37).

These results are consistent with extant research showing that bipolar disorder renders high medical service utilization and associated costs for both patients and their insurance companies (10,38,39). Consequently, general medical providers may be treating symptoms or comorbid conditions of bipolar disorder, such as depressed mood, insomnia, fatigue, agitation, cardiovascular disease (40), or respiratory disorders (7), as well as observing patterns of increased treatment utilization without necessarily being aware of the bipolar diagnosis. This highlights the possibility of fragmented care for this group of patients, who often have multiple symptoms; coordinated prevention management of bipolar disorder would likely decrease its financial burden and improve the likelihood of sustained remission (10,41).

Interpretation of these results must be considered within the context of the methodological limitations. First, the CSI does not differentiate between using multiple services and using the same service multiple times, nor does it capture reasons for seeking a service or distinguish between general and specialized care. Second, the study relied on patient self-reports of service utilization and did not assess whether participants used services appropriate for their individual needs. Observations were not purely naturalistic, given that they were collected in the context of a clinical trial, and thus limit the generalizability of the findings. This context could influence service use, either increasing it as frequent study visits made participants more aware of health care needs or decreasing it as the clinical trial offered consistent clinical attention. Furthermore, although diverse, the study population comprised individuals willing to participate in research and thus cannot fully represent the entire population with bipolar disorder. The largely null results for the use of counseling services may be accounted for by a potential statistical power issue in that few participants sought such services and did so infrequently. Finally, the direction of causality of these relationships is speculative.

In short, our data show that outpatients with bipolar disorder sought medical and counseling services at specific times in their course of illness and overall health. Results suggest that treatment providers should pay special attention to characteristics with low mutability (middle age, recent immigration, or current unemployment) to ensure that persons have equitable access to health services (29). Data also highlight characteristics with higher mutability, such as worsening manic symptoms and high burden of side effects, to help providers determine areas of focus in their treatment planning and evaluations. Overall, these analyses helped to clarify the behavioral health service model for bipolar disorder by offering data on both population characteristics (predisposing and need factors) and health behavior (personal health practices and use of health services); this information will ultimately help to optimize overall outcomes (perceived and evaluated health outcomes and consumer satisfaction) (28,37).

This study was funded by contract NO1MH80001 from the National Institute of Mental Health.

Dr. Sylvia was a shareholder in Concordant Rater Systems and serves as a consultant for United Biosource Corporation and Clintara. She receives royalties from New Harbinger. Dr. Iosifescu is a consultant for CNS Response and Servier. Dr. Friedman receives grant support from AstraZeneca Pharmaceuticals, Medtronics, Novartis, Repligen, Roche, St. Jude Medical, and Takeda. He receives royalties from Springer. Dr. Ketter receives research support from AstraZeneca, Cephalon, Eli Lilly and Company, Pfizer, and Sunovion Pharmaceuticals. He receives consultant fees from Allergan, Avanir Pharmaceuticals, Bristol-Myers Squibb Company, Cephalon, Forest Pharmaceuticals, Janssen Pharmaceutica Products, Merck & Co., Sunovion, and Teva Pharmaceuticals. He has received lecture honoraria from Abbott Laboratories, AstraZeneca, GlaxoSmithKline, and Otsuka Pharmaceuticals and receives publication royalties from American Psychiatric Publishing. In addition, Dr. Ketter’s spouse is an employee of and holds stock in Janssen. Dr. Reilly-Harrington receives royalties from Oxford University Press and the American Psychological Association and serves as a consultant for United Biosource Corporation. Dr. Leon served on independent data and safety monitoring boards for AstraZeneca, Sunovion, and Pfizer. He served as a consultant and advisor to MedAvante and Roche and had equity in MedAvante. Dr. Calabrese receives research funding or grants from the following private industries or nonprofit funds: Brain and Behavior Research Foundation (formerly NARSAD), Cleveland Foundation, and Stanley Medical Research Institute; he receives research grants from Abbott, AstraZeneca, Cephalon, GlaxoSmithKline, Janssen, Eli Lilly, and Lundbeck; he serves on the advisory boards of Abbott, AstraZeneca, Bristol-Myers Squibb, Dainippon Sumitomo Pharma, Forest, France Foundation, GlaxoSmithKline, Janssen, NeuroSearch, OrthoMcNeil, Repligen, Schering-Plough, Servier, Solvay/Wyeth, Takeda, and Supernus Pharmaceuticals; and he reports continuing medical education activities with AstraZeneca, Bristol-Myers Squibb, France Foundation, GlaxoSmithKline, Janssen, Johnson & Johnson, Schering-Plough, and Solvay/Wyeth. Dr. Ostacher has served as a consultant for Alexza Pharmaceuticals, Bristol Myers Squibb, Eli Lilly, Janssen, Otsuka, and Sunovion. Dr. Thase has, during the past three years, been an advisor or consultant to Alkermes, Allergan, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Forest Laboratories, GlaxoSmithKline, Janssen, Lundbeck, MedAvante, Merck, Mylan, Neuronetics, Otsuka, Pamlab, Pfizer, PharmaNeuroboost, Roche, Shire, Sunovion, Takeda, and Teva. During the same time frame, he received honoraria for continuing education talks that were supported by AstraZeneca, Bristol-Myers Squibb, Merck, and Pfizer, and he has received research grants from Alkermes, AstraZeneca, Eli Lilly, Forest, GlaxoSmithKline, Otsuka, PharmaNeuroboost, and Roche. Dr. Nierenberg is a consultant for Abbott Laboratories, AstraZeneca, Basilea, BrainCells Inc., Brandeis University, Bristol-Myers Squibb, Cephalon, Corcept, Eli Lilly, Forest, Genaissance, GlaxoSmithKline, Innapharma, Janssen, Jazz Pharmaceuticals, Lundbeck, Merck, Novartis, PamLabs, Pfizer, PGx Health, Ridge Diagnostics, Roche, Sepracor, Schering-Plough, Shire, Somerset, Sunovion, Takeda, Targacept, and Teva. He is a stakeholder in Appliance Computing, Inc. (MindSite); Brain Cells, Inc.; and InfoMed (potential share of income). He receives research support from Brain and Behavior Research Foundation, Bristol-Myers Squibb, Cederroth, Cyberonics, Elan, Forest Pharmaceuticals, GlaxoSmithKline, Janssen, Lichtwer Pharma, Eli Lilly, Mylan, Pamlabs, Pfizer, Shire, Stanley Foundation, and Wyeth-Ayerst. Honoraria include MGH Psychiatry Academy. He receives other income from CRICO for legal case reviews, from MBL Publishing for past services as Editor-in-Chief of CNS Spectrums, from Slack Inc. for services as associate editor of Psychiatric Annals, and from Belvoir Publications for serving on the editorial board of Mind Mood Memory. He has joint copyright ownership with MGH for the Structured Clinical Interview for MADRS and Clinical Positive Affect Scale. He receives additional honoraria from ADURS, American Society for Clinical Psychopharmacology, AstraZeneca, Biomedical Development, Brandeis University, East Asian Bipolar Forum, Eli Lilly, Forest, Harold Grinspoon Charitable Foundation, Health New England, International Society for Bipolar Disorder, Janssen, Mid-Atlantic Permanente Research Institute, University of Pisa, University Texas Southwest at Dallas, University of Wisconsin–Madison, Up-to-Date, and Zucker Hillside Hospital. The other authors report no competing interests.