Petri Arvilommi Treatment, Adherence, and Disability in Bipolar Disorder ACADEMIC DISSERTATION To be presented with the permission of the Faculty of Medicine, University of Helsinki, for public examination at the HUCH Psychiatry Centre, Christian Sibelius Auditorium, Välskärinkatu 12, on 10th June 2016, at 12 noon. Department of Psychiatry University of Helsinki Helsinki, Finland Helsinki 2016 Supervisors Professor Erkki Isometsä, M.D., Ph.D. Department of Psychiatry, Faculty of Medicine University of Helsinki Helsinki, Finland and Docent Kirsi Suominen, M.D., Ph.D. Department of Mental Health and Substance Abuse, City of Helsinki, Social Services and Health Care Helsinki, Finland Reviewers Professor Jyrki Korkeila, M.D., Ph.D. Faculty of Medicine, University of Turku, Turku, Finland and Associate professor Olli Kampman, M.D., Ph.D. School of Medicine, University of Tampere Seinäjoki Hospital District, Department of Psychiatry Tampere, Finland Opponent Professor Esa Leinonen, M.D., Ph.D. School of Medicine, University of Tampere Dissertationes Scholae Doctoralis Ad Sanitatem Investigandam Universitatis Helsinkiensis ISBN 978-951-51-2205-6 (pbk.) ISBN 978-951-51-2206-3 (PDF) ISSN 2342-3161 (print) ISSN 2342-317X (online) http://ethesis.helsinki.fi T a m p e r e , F i n l a n d “The endless questioning finally ended. My psychiatrist looked at me, there was no uncertainty in his voice. “Manic-depressive illness.” I admired his bluntness. I wished him locusts on his lands and a pox upon his house. Silent, unbelievable rage. I smiled pleasantly. He smiled back. The war had just begun.” Kay Redfield Jamison “An Unquiet Mind” (1995) Abstract Petri Arvilommi. Treatment, Adherence, and Disability in Bipolar Disorder. This study is part of a collaborative bipolar research project between the Unit of Mental Health of the National Institute for Health and Welfare, Helsinki (the former Department of Mental Health and Alcohol Research of the National Public Health Institute, Helsinki) and the Department of Psychiatry, Jorvi Hospital, Helsinki University Central Hospital (HUCH), Espoo, Finland. The Jorvi Bipolar Study (JoBS) is a prospective, naturalistic cohort study of 191 secondary-level care psychiatric in- and outpatients with a new episode of DSM-IV bipolar disorder (BD). Overall, the study involved screening 1,630 adult patients (aged 18-59 years) using the Mood Disorder Questionnaire (MDQ) for symptoms of bipolar disorder in the Department of Psychiatry, Jorvi Hospital, from January 1, 2002, to February 28, 2003, for a possible new episode of bipolar disorder. A clinical diagnosis of ICD-10 schizophrenia was an exclusion criterion for screening. The 490 consenting patients were interviewed with a semi-structured interview (SCID- I/P). Thereby, 191 patients were diagnosed with an acute phase of DSM-IV BD and included in the study. The patients participating were interviewed again 6 and 18 months after baseline. The course of the disease, with timing and durations of different phases, was examined by gathering all available data, which were then combined in the form of a graphical life chart. Observer- and self-reported scales were included at baseline and at both follow-up assessments. Also, the treatments provided were investigated at baseline and at both follow-up interviews. The aim in the first study was to investigate the adequacy of acute phase pharmacotherapy received by psychiatric in- and outpatients with a research diagnosis of BD I or BD II, including patients with and without a clinical diagnosis of BD. Information about treatments received during the index acute episode was gathered in the interview and from psychiatric records. Definitions of adequate acute-phase pharmacotherapy were based on published treatment guidelines. Only 42% of all 191 patients and 65% of those diagnosed with bipolar disorder received adequate treatment for the acute index phase. Clinical diagnosis of bipolar disorder was the factor most strongly independently associated with adequate treatment. In addition, rapid cycling, polyphasic index episode, or depressive index phase independently predicted inadequate treatment. Outpatients received adequate treatment markedly less often than inpatients. Lack of attention to the longitudinal course of the illness was another major problem area of treatment. Next, our aim was to investigate the adequacy of the maintenance-phase pharmacotherapy received during the first maintenance phase after an acute episode, following the same patients as in the first study. We defined adequate maintenance-phase pharmacotherapy based on published treatment guidelines. Of 4 the patients with a maintenance phase in follow-up, adequate maintenance treatment was received by 75% for some time, but by only 61% throughout the maintenance phase and for 69% of the total maintenance time. Having adequate maintenance treatment throughout the maintenance phase was most strongly independently associated with having a clinical diagnosis of BD. In addition, inpatient treatment, rapid cycling, and not having a personality disorder predicted receiving adequate maintenance treatment throughout the maintenance phase. In addition, we investigated the continuity of attitudes toward and adherence to various types of psychopharmacological and psychosocial treatments among psychiatric in- and outpatients with BD I or II. During the 18-month follow-up, a quarter of the patients using mood stabilizers or atypical antipsychotics discontinued medication by their own decision, and of the medications continued, a third were not used regularly enough to provide a benefit. Overall, more than half of BD patients either discontinued pharmacotherapy or used it irregularly. The highest risk for discontinuing pharmacotherapy was present when the patients were depressed. Also, a quarter of the patients receiving psychosocial treatments did not adhere to the treatment. The main reasons patients gave for nonadherence toward pharmacological treatment were side-effects, lack of motivation, and a negative attitude toward the offered treatment; for individual/supportive psychotherapy, the reasons included practical barriers to coming to sessions and lack of motivation. Rates of nonadherence to mood stabilizers and antipsychotics did not differ, but the predictors did. Last, we investigated the prevalence and clinical factors predicting the granting of a long-term disability pension for patients with BD. We used register data to gather precise information on the pensions granted and their timing. During the 18-month follow-up after an acute episode, a quarter of the patients belonging to the labor force were granted a disability pension. Higher age, male gender, depressive index episode, comorbidity with generalized anxiety disorder (GAD) or avoidant personality disorder, and a higher number of psychiatric hospital treatments all independently predicted the granting of a disability pension. Moreover, patients’ subjective estimations of their vocational ability were surprisingly accurate in forecasting the granting of a future disability pension. In addition, the depression-related cumulative burden and the proportion of time spent in depression during the follow-up were important predictors. However, the predictors may vary depending on the subtype of illness, gender, and age group of the patient. Keywords: bipolar disorder, treatment, maintenance, adherence, disability, disability pension 5 Tiivistelmä Petri Arvilommi. Treatment, Adherence, and Disability in Bipolar Disorder. Tämä tutkimus on osa Terveyden ja Hyvinvoinnin Laitoksen Mielenterveysyksikön ja Uudenmaan sairaanhoitopiirin Jorvin sairaalan psykiatrian tulosyksikön kaksisuuntaisen mielialahäiriön seurantatutkimusta (Jorvi Bipolar Study, JoBS), jossa seurattiin 191 ajankohtaisesta (DSM-IV) mielialajaksosta kärsivää psykiatrisen erikoissairaanhoidon avohoito- ja sairaalapotilasta. Tutkimusta varten Jorvin psykiatrisessa erikoissairaanhoidossa seulottiin 1.1.2002 alkaen 28.2.2003 saakka 1630 potilasta (iältään 18-59 vuotta), kaksisuuntaisen mielialahäiriön oireiden suhteen. Kliininen ICD-10 skitsofreniadiagnoosi oli poissulkukriteeri seulontaan. Tutkimushaastatteluun suostui 490 potilasta, jotka haastateltiin puolistrukturoidulla haastattelumenetelmällä (SCID-I/P). Tutkimukseen otettiin 191 potilasta, joilla oli diagnosoitu akuutissa vaiheessa oleva kaksisuuntainen mielialahäiriö. Potilaat haastateltiin uudelleen 6- ja 18- kuukautta tutkimukseen ottamisen jälkeen. Taudin kulku, vaiheiden ajoitus ja kesto tutkittiin keräämällä kaikki käytettävissä oleva tieto, joka koottiin yksityiskohtaiseksi graafiseksi kuvaajaksi, oirekortiksi. Sekä alku- että seurantahaastatteluihin kuului tutkijan ja potilaan täyttämiä tutkimuslomakkeita. Myös määrätyt hoidot tutkittiin sekä alku- että seurantahaastatteluissa. Tutkimuksen ensimmäinen tavoite oli selvittää miten asianmukaista akuutin vaiheen lääkehoitoa saavat psykiatriset sairaala- ja avohoitopotilaat, joille on asetettu tutkimusdiagnoosiksi kaksisuuntainen mielialahäiriö tyyppi I tai II, mukaan lukien ne potilaat joilla ei ole kliinistä kaksisuuntaisen mielialahäiriön diagnoosia. Asianmukaisen lääkehoidon määritelmät perustuivat hoitosuosituksiin. Vain 42% kaikista 191 potilaasta ja 65% niistä, joilla oli kliininen kaksisuuntaisen mielialahäiriön diagnoosi, saivat asianmukaista hoitoa akuuttivaiheessa. Kliininen diagnoosi oli tärkein asianmukaista hoitoa itsenäisesti ennustava tekijä. Sen lisäksi asianmukaista hoitoa itsenäisesti ennustivat tiheäjaksoisuus, monivaiheinen