The impact of personality disorders on treatment outcome in bipolar disorder: A review

Transcription

1 Personality and Mental Health 1: 2 13 (2007) Published online in Wiley InterScience ( The impact of personality disorders on treatment outcome in bipolar disorder: A review PETER J. BIELING, SHERYL M. GREEN and GLENDA MACQUEEN, Department of Psychiatry and Behavioural Neurosciences, McMaster University and St. Joseph s Healthcare, Hamilton, ON ABSTRACT Bipolar disorder (BD) is a chronic psychiatric illness for which there are a number of effi cacious and effective treatments. However, for many sufferers recovery is incomplete or tenuous. Factors associated with poor outcomes in the disorder are of special interest, and comorbidity of BD with personality disorder (PD) has been proposed as a possible predictor of poor outcome. We reviewed available studies (n = 12) in the literature that specifi cally assessed the impact of personality psychopathology on illness outcomes in BD including functioning, response to treatment and suicidality. Quality of methodology, assessment methods and number of participants in studies were highly variable. Despite these variations in study quality, the presence of a PD was robustly associated (usually medium size effects) with a worse outcome in BD. Patients with BD and a diagnosis of PD are more likely to be hospitalized, require more time to achieve symptom stabilization, have more chronic impairments in occupational and social functioning, are less compliant to medication, have greater levels of suicidality and utilize more psychiatric services than patients with BD alone. The implications of these fi ndings for further research and clinical care in BD are discussed. Copyright 2007 John Wiley & Sons, Ltd. Bipolar disorder (BD) is a common psychiatric illness; recent estimates suggest that BD affects approximately 2% of the population, although estimates of the lifetime rate of bipolar spectrum disorder approach 5% (Merikangas et al., 2007). The World Health Organization has reported that BD is one of the costliest of all medical disorders in terms of negative impact on functioning (Murray & Lopez, 1997). Various methods of treatment, including mood stabilizers and at least some psychosocial interventions have acknowledged efficacy; however, longitudinal studies have shown substantial relapse rates, residual symptoms and impairment in functioning, despite access to effective treatments (Bieling & MacQueen, 2005). Therefore, factors that might predict differences in outcomes in BD are of special interest to researchers and clinicians. One such candidate predictor is disturbances of personality or character. As this area is still a relatively novel one for researchers and clinicians interested in BD, a more longstanding and compelling literature in major depressive disorder (MDD) is instructive. Within MDD, a considerable body of evidence exists suggesting that a diagnosed comorbid personality disorder (PD) predicts slower treatment

2 Bipolar disorder and personality comorbidity 3 response, slower recovery of social function on discharge from hospital (compared with patients without a PD) and less improvement with psychotherapy (e.g. Frank, Kupfer, Jacob, & Jarrett, 1986; Weissman, Prusoff, & Klerman, 1978). A recent meta-analysis of this literature involving 34 studies suggested that the presence of PD doubles the probability of a poor outcome in depression (Newton-Howes, Tyrer, & Johnson, 2006). Despite the fi nding that personality features are poor prognostic indicators in MDD, evidence on the impact of PD in BD is not nearly as well developed, although there is now a reasonable body of studies available. The purpose of the present review was to examine the impact of comorbid PD with respect to both acute, and where possible, long-term clinical outcome in BD. Studies were sought with the use of a Pub Med literature search with the search terms bipolar and personality dated from 1970 until March We then reviewed abstracts for all identified papers to determine whether the study was data driven and included some measure of outcome (vs. e.g. studies of comorbidity rates or theoretical papers). Because the number of studies in this area remains relatively discrete, we defi ned outcomes as broadly as possible to include symptoms, impairment, functioning or sentinel events (i.e. suicide). We also included naturalistic studies that were largely correlational in nature as well as controlled trials that involved the implementation of a study-related treatment. Any study that allowed for some differentiation between BD patients with and without PD was included so long as the study assessed an illness outcome variable. A narrative review was employed as a means of describing these studies as opposed to a meta-analysis for two reasons. First, the relatively small number of studies that were available (n = 12) at the outset required subgrouping into categories to be meaningful; these categories were PD and functional or psychosocial impairment (n = 5), PD comorbidity and response to pharmacotherapy (n = 5), and PD/BD comorbidity and suicidality (n = 2). Thus, the number of studies in each category was not suitable for meta-analysis. Further, there were a number of qualitative differences between methodologies across studies that would not allow for an appropriate comparison or grouping for meta-analysis. Following this narrative review of the studies, we offer some observations about the methodology of this work, future directions and implications for treatment. In addition, the studies we reviewed are presented in Table 1 to summarize the effect of PDs on outcome in BD. For each study that is described in the sections that follow, Table 1 outlines the study question, design, time frame, sample, PD measurement and results. Methods Functional/psychosocial impairment In a series of studies that are among the fi rst in the area, Dunayevich et al. (1996, 2000) investigated the prevalence of PDs in patients with fi rst (n = 33) and multiple episodes (n = 26) of mania and evaluated the impact of PDs on treatment outcome in BD over a one-year time period. They assessed 56 patients who were hospitalized with a diagnosis of mania or mixed state using the Structured Clinical Interview for Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition (DSM-IV) Axis II (SCID-II; First, Spitzer, Gibbon, & Williams, 1997) to obtain diagnoses of PD. Inclusion criteria for this study were relatively broad; participants were required to be between years old, able to communicate in English and reside within the study area. Patients were excluded if their psychiatric symptoms resulted entirely from acute drug or alcohol intoxication or withdrawal, or acute medical illness as determined by medical evaluation and rapid symptom resolution after the medical event. Patients with no prior psychiatric hospitalizations or treatment for mania were included in the fi rst-episode group while the remaining participants were classified as having

3 4 Bieling et al. Table 1: Available literature summary: The effect of personality disorders on outcome in bipolar disorder Author Study question Design Time frame Sample PD measurement Results Abou-Saleh, 1983 Is response to lithium Combination Maintaince period 36 BD (18 responders; Eysenck Personality Lithium non-responders associated with retrospective of 2 years and 18 non-responders) Questionnaire and had higher neuroticism personality factors and prospective current Foulds Personality and lower dominance in BD? questionnaires Deviance Scale scores than responders. Bieling et al., 2003 Are Axis II features Prospective Followed for an 87 BD Type I and SCID-II Screening High scores on associated with poor naturalistic average of 3.4 Type II outpatients Questionnaire PD scales distinguished long-term outcome follow-up years symptomatic from euthymic in BD? patients in long-term follow-up. Colom et al., 2000 What clinical factors Retrospective 2-year naturalistic 144 BD Type I SCID-II Patients with PD were over 2 are associated with self-report follow-up study 56 BD Type II times more likely to be poorly non-compliance? compliant. Dunayevich et al., Is treatment outcome Prospective Followed for 1 year 56 BD Type I fi rst SCID-II prior to Patients with PD are 5 more 1996, 2000 worse in BD patients naturalistic post-hospital episode and discharge likely to have had past with PDs compared follow-up discharge multiple episode hospitalizations; 35% of to BD alone? inpatients patients with PD attained syndromic recovery compared to 69% without PD. Garno et al., 2005 Do comorbid PDs Retrospective Reported lifetime 73 BD Type I and SCID-II Cluster B comorbidity was impact on course, interview history of suicide 27 BD Type II associated with significantly outcome and risk of attempts more lifetime suicide attempts. lifetime suicide As such, cluster B features may attempts for patients directly and independently with BD? contribute to suicide risk for some BD patients. Gasperini et al., Do comorbid PDs Prospective Minimum 24-month 112 (58 unipolar and SIDP Co-existence of PD s was related 1993 influence relapse of naturalistic period of lithium 54 bipolar), 58 = to worse recurrence indices on mood disorders on follow-up treatment 1 PD, 18 = multiple lithium treatment in both lithium therapy? PD s, 36 = no PDs unipolar and BD compared to those without a PD. Presence of histrionic PD with BD or unipolar depression predicted the worse recurrence indices.

4 Bipolar disorder and personality comorbidity 5 Table 1: (Continued) Author Study question Design Time frame Sample PD measurement Results Henry et al., 1999 Does affective Retrospective Assessment and 72 BD I French version of the Positive association between temperament in BD interview questionnaires Semi-structured depressive temperament scores patients impact administered Interview of and outcome prognosis? with no time depressive and followed hyperthymic temperament developed by Akiskal and Mallya (1987) Lembke et al., What determinants Retrospective 3 months 500 BD patients Treating psychiatrists BD patients with PDs (80% vs influence psychosocial interview (74% Type I, 24% assessment using 20%)reported more service utilization in Type II) the ADE psychosocial services in the 3 BD patients? months. Leverich et al., What clinical variables Combination 2.8 years 648 BD I and BD II PDQ-4+ Cluster B predictor of past serious 2003 influence serious retrospective retrospective and suicide attempts suicide attempts in and prospective current interview patients with BD? Loftus & Jaeger, Are comorbid PDs Prospective 1 year 51 BD Type I (n = 4 SCID-II Presence of a PD or maladaptive 2006 predictive of naturalistic inpatients; n = 47 trait scores was associated with functional morbidity follow-up outpatients) more impaired functioning in in BD I? occupational, residential and social/leisure outcome domains. Preston et al., What is the response to Retrospective Interviewed an 35 BD SCID-II BPD dimensions improved with 2004 treatment with analysis of RCT average of 15.3 treatment in both patients lamotrigine in patients months following groups (with formalbpd and with BD and comorbid the original study without). Trend for comorbid BD/BPD? BD patients required a second psychoactive medication. Swartz et al., 2005 Are medication treatment Matched case Weeks to 12 BD I and BPD SCID-II interview Treatment course may be longer outcomes in BD patients control stabilization 58 BD I only in patients suffering from both with a PD and BD only (maximum 97 BD Type I and BPD compared patients different? weeks) to BD only. SCID-II, Structured Clinical Interview for DSM-IV Axis II; SIDP, Structured Interview for DSM-IV Personality; ADE, Affective Disorder Evaluation; PDQ-4+, Personality Diagnostic Questionnaire-4+; RCT, Randomized Control Trial.

5 6 Bieling et al. multiple episodes. Patients were interviewed on the SCID-II shortly before discharge, and the investigators specifically noted that patients were judged sufficiently recovered from an affective episode that they were able to answer questions using their pre-morbid function as the standard reference. Using this method, 48% of patients received a diagnosis of a PD. There was no difference in age, sex distribution, education or employment status, substance use disorder, mania or depression rating scale scores of the patients with or without PD. However, PDs were significantly more common in the multiple-episode group than in the fi rst-episode group and patients with a PD diagnosis were five times more likely to have had a past hospitalization than those with no PD diagnosis, despite the fact that the groups did not differ by age. Outcome assessments were scheduled at 2, 6 and 12 months after discharge. To assess recovery at each visit, the interviewers concentrated on change points that occurred during the interval (i.e. times when symptoms or function improved or worsened). Following the index episode, the presence of a PD was associated with a lack of syndromic recovery, with only 35% of patients with a PD attaining syndromic recovery compared to 69% of patients without a PD. Syndromic recovery was defi ned as eight contiguous weeks during which the patient no longer met criteria for a manic, mixed or depressive syndrome. Only 12% of patients with a PD achieved symptomatic recovery while 38% of patients without a PD achieved symptomatic recovery. Symptomatic recovery consisted of eight contiguous weeks during which the patient experienced minimal to no psychiatric symptoms, assessed using the Young Mania Rating Scale (YMRS) and the Hamilton Rating Scale for Depression (HAM- D). Finally, only 10% of patients with PD achieved full functional recovery over the one year of followup compared to 31% of patients without a PD. Functional recovery required a return to pre-morbid levels of function for at least eight contiguous weeks. The authors note several features that may have contributed to the poor outcome in the patients with co-morbid PD, including compliance as a mediating factor and the fact that more patients with PD had multiple past episodes of illness. Based on these results, the authors suggest that prospective long-term studies of fi rst-episode BD patients also consider the course of personality problems and the development of maladaptive behavioural patterns in response to repeated illness episodes. Henry et al. (1999) conducted another study addressing similar outcome variables but from a personality temperament perspective rather than a PD perspective. A total of 72 patients with a diagnosis of BD Type I based on the French version of the Diagnostic Interview for Genetic Studies were assessed when remitted using the depressive temperament (DT) and hyperthymic temperament (HT) scales developed by Akiskal and Mallya (1987). These two scales were composed of 22 items about usual mood, cognition, psychomotor agitation or retardation, personal interrelations, attitudes to social norms, sleep needs and sexual appetite. To be classified as DT or HT, at least five items had to be met and the categorization of DT or HT was mutually exclusive. Regression analyses were conducted, controlling for age, sex and educational attainment. The authors found a positive association with DT scores and outcome as assessed by total number of past manic or depressive episodes. In addition, there was a negative correlation between DT score and percentage of manic episodes but a positive correlation between HT score and percentage of manic episodes. Overall, a high score on the DT scale was associated with a greater lifetime number of mood-related episodes, a high percentage of depressive episodes and a history of suicide attempts. As such, this study demonstrates a continuum between temperament and polarity of episodes and a better prognosis for patients presenting with hyperthymic traits. Bieling et al. (2003) used a life-charting method to determine the extent to which a range of Axis II features, measured in a continuum fashion, were associated with poor long-term outcome in a group of individuals with BD. The inclusion criteria for the sample were (1) age between years old and (2) diagnosed with BD Type I or II as assessed

6 Bipolar disorder and personality comorbidity 7 by SCID. Patients with substance abuse or dependence within six months of study entry were excluded, which might be relevant to the generalizability of the sample. In total, 87 BD Type I and II patients were included in this study. Prior to entry into the life-charting study, all patients were administered the SCID-II screening questionnaire. Patients were followed regularly and treated according to published guidelines for pharmacologic treatment for an average of 3.4 years (standard deviation (SD) = 13 months; 76% female; mean age = 43.0, SD = 10.92). The course of illness was documented using a modified life-charting technique based on the National Institute of Mental Health (NIMH) life-charting method that allows for a graphical representation of the longitudinal course of mood disorders (e.g. Roy-Byrne, Post, Uhde, Porcu, & Davis, 1985). The outcome year served as the primary dependent variable in which patient symptoms and functioning were assessed every 3.9 weeks on average (SD = 2.4 weeks). Better outcomes on symptom severity and functioning were noted for patients with lower scores on 7 out of 10 PD categories; Cluster A (paranoid, schizoid, schizotypal) PD symptoms best distinguished euthymic and symptomatic patients. Consistent with previous fi ndings in MDD, the presence of PD traits predicted negative outcome over this relatively long-term follow-up. In light of these fi ndings, the authors suggest that in situations where standard treatment for BD does not result in sufficient improvement, Axis II issues need to be systematically assessed and may need to be included as a specific focus for treatment. Lembke et al. (2004) examined the determinants of psychosocial service utilization in adults with BD using a retrospective approach. Their sample included the fi rst 500 patients admitted to the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), a multi-centre study of the course and outcome of BD funded by the NIMH. The primary assessment tool to identify psychosocial service utilization in BD was the Care Utilization form, an instrument designed to quantify service utilization in this population. Adjunctive psychosocial service utilization was recorded and defi ned as having at least one session with a psychologist, social worker, counselor or self-help group in the three months prior to enrolment in the study. The study then employed a combination of naturalistic data and randomized trial data to assess somatic and psychosocial intervention strategies in the treatment of all phases of BD. Participants in this study met DSM-IV criteria for any subtype of BD (including BD not otherwise specified and cyclothymia). The Affective Disorder Evaluation (ADE) questionnaire, Mini International Neuropsychiatric Interview, YMRS, and the Montgomery Asberg Depression Rating Scale were used to determine clinical status at study entry, severity of illness, number of prior affective episodes and presence of comorbid psychiatric disorders. Determination of Axis II comorbidity was based on the treating psychiatrist s assessment of Axis II pathology using the ADE rather than the SCID-II. The majority of the sample was female (60%), mean age 41.9 (SD = 12.8), with a diagnosis of BD Type I (74%). Of the 440 patients, 54% were receiving adjunctive psychosocial services in the three months prior to enrolling in STEP. The authors found that BD patients with PDs (80% of the sample), alcohol/ drug abuse disorders (76%) and anxiety disorders (60%) received more psychosocial services in the three months prior to study entry than those without. Interestingly, significant differences in psychosocial service utilization between the STEP- BD sites suggested that differences in service availability or differences in treatment models played a significant role in patients usage of mental health services in this sample. As a result, the authors suggest that these variables should be fully operationalized in future studies. Loftus and Jaeger (2006) examined whether comorbid PDs and other clinical factors were predictive of functional morbidity over a one-year of follow-up. Their sample consisted of 51 BD Type I inpatients and outpatients receiving services at a large suburban psychiatric hospital (mean age =

7 8 Bieling et al years, SD = 2.4; 43% male; mean hospitalizations = 7.1, SD = 5.3). PD trait scores were calculated by summing the number of items on the SCID-II that were endorsed as present across each of the 12 DSM-IV PDs. A total of 45% of the sample met the criteria for PD and patients with a PD reported higher levels of residual symptoms at the time of assessment. The most frequently diagnosed PDs were cluster B disorders (28%), particularly borderline PD (20%). Approximately one year after their psychiatric hospitalizations, patients were administered the Hamilton Rating Scale for Depression (HAM-D) (Hamilton, 1960) and the Clinician-Administered Rating Scale for Mania (Altman, Hedeker, Janicak, Peterson, & Davis, 1994) to measure symptomatic outcomes. The presence of a PD or maladaptive trait scores was associated with more impaired functioning in occupational, residential and social/leisure outcome domains as evaluated by the Multidimensional Scale for Independent Functioning (Jaeger, Berns, & Czobor, 2003). The authors note that older age and residual depressive symptoms were also important predictors of impaired residential and social/ leisure outcomes. As such, the authors suggest that interventions targeting personality issues and subsyndromal depression may be fun damental to improving psychosocial outcomes in BD. In summary, these studies suggest that comorbidity of BD and PD was associated with poor prognostic outcome (see Table 1). For instance, studies found that the presence of a PD in patients with BD was associated with a lack of syndromic recovery and such patients are much less likely to have a full functional recovery. Further, BD patients with PDs tend to have a higher rate of alcohol/drug abuse disorders, anxiety disorders and tend to receive more psychosocial services than those without. Effectiveness of pharmacotherapy in the presence of comorbid BD and PD Given the central role of mood stabilizers and other medications in the treatment of BD, the impact of PDs on medication-related outcomes, including adherence, has been of some interest for BD researchers. Abou-Saleh (1983) retrospectively evaluated response to lithium in patients with BD, operationally defi ning lithium responders as those who had no recurrence of episodes after six months of lithium treatment. Lithium non-responders had at least one episode after the fi rst six months of lithium treatment. All participants in the study (regardless of response) were maintained on lithium (plasma levels between mmol/l) for a minimum of two years. An episode was defi ned as significant depressive or manic symptoms of no less than four weeks duration and of a severity that necessitated admission to hospital or prescription of extra medication on an outpatient basis. Of the 73 patients that satisfied the criteria for lithium responders or non-responders, 53 agreed to participate and ultimately 36 (18 responders and 18 nonresponders) were evaluated. Lithium non-responders had higher neuroticism, as assessed on the Eysenck Personality Questionnaire, and lower dominance scores, measured on Foulds Personality Deviance Scale, than responders. The authors suggested that patients with BD who do not respond to lithium should be evaluated for confounding personality difficulties that might be helped by adjunctive psychological treatment. Gasperini, Scherillo, Manfredonia, Franchini, and Smeraldi (1993) examined rates of relapse in a sample of participants treated with lithium, hypothesizing that the presence of PD would have an impact on the level of prophylaxis provided by this mood stabilizer. They evaluated the rate of overall episodes of illness (both episodes of depression and mania) over a range of months of lithium treatment. Participants were recruited from an outpatient lithium clinic, and the sample included 100 patients with recurrent major depression and 113 patients with BD. Participants were considered to have a relapse when they met DSM- III-R criteria for an episode of mania or depression after being in remission for at least eight consecutive weeks. The coexistence of PDs with BD was related to a larger number of relapses, and this

8 Bipolar disorder and personality comorbidity 9 fi ndi ng wa s also true in unipolar depression. Further, the presence of histrionic PD in particular was associated with high risk of relapse. Finally, it did not appear that the results were mediated by medication adherence, as presence of PD had no impact on level of adherence to lithium treatment in this monitored sample. Preston, Marchant, Reimherr, Strong, and Hedges (2004) retrospectively assessed DSM-IV dimensions of Borderline Personality Disorder (BPD) pre- and post-treatment with lamotrigine in 35 patients with BD. Specifically, they examined the presence of BPD dimensions using items on the SCID-II. Exclusion criteria for the sample of participants included rapid cycling, recent history of alcohol or drug abuse, or PD severe enough to interfere with the study protocol, all factors which could affect the generalizability of the results. All patients that the authors could locate from the original study (35 of 56) were re-interviewed and the SCID-IV was used to reconfi rm the diagnosis of BD Type I. The Axis I and PD interviews were conducted an average of 15.3 months following the original study. A total of 40% of the sample met the criteria for BPD. In addition to changes in symptoms of mood disorder on Axis I, the researchers were also interested in changes in BPD symptomatology as a result of treatment with lamotrigine. The authors found that BPD dimensions improved significantly with treatment in both patient groups (with formal BPD and without) and corresponded with response in bipolar symptoms. Six (43%) of the comorbid patients endorsed three or fewer criteria of BPD during treatment with lamotrigine. Further, there was a trend for comorbid patients to require a second psychoactive medication in addition to lamotrigine during extended treatment. The authors acknowledged the difficulty in interpreting the results as criteria for BPD and improvement were assessed retrospectively. The association between pharmacological treatment compliance and PD in BD was studied in detail by Colom et al. (2000). They assessed 144 patients with BD Type I and 56 patients with BD Type II who were enrolled in a two-year naturalistic follow-up study. All patients received the Spanish version of the SCID-II to assess rate and type of PD. Patients with HAM-D scores higher than 8 or YMRS scores higher than 6 at the time of the compliance interview were excluded from the study to ensure that compliance-related behaviour would not be a consequence of clinical state. Compliance was assessed by a clinical and compliance-focused interview with the patient and also with a fi rst-degree significant relative or partner in addition to plasma concentration measures of mood stabilizers that were assessed during the preceding two years. Patients were divided into those with good compliance (n = 121) and poor compliance (n = 79). A higher proportion of patients in the poor compliance group (39.2%) had Axis II comorbidity compared to the good compliance group (17.4%), and the presence of a PD was more predictive of poor compliance than substance abuse, socio-economic status, marital status, education level or specific medications prescribed (Colom et al., 2000). The authors concluded that patients with BD and comorbid PDs should be carefully monitored for treatment compliance as they may have more difficulties in recognizing prodromal symptoms and following medical advice. Finally, Swartz, Pilkonis, Frank, Proietti, and Scott (2005) compared medication treatment outcomes in a sample of patients who met standardized diagnostic criteria for both BD Type I and BPD (n = 12) to those who met criteria for BD Type I only (n = 58). The design involved following patients with algorithm derived pharmacotherapy and psychotherapy until stabilization occurred, with stabilization defi ned as four consecutive weeks with a calculated average totaling less than or equal to 7 on the 17-item version of the HAM-D and Bech-Rafaelsen Mania Scale while on a constant medication regimen. Psychotherapy was in the form of Interpersonal and Social Rhythm Therapy. Participant inclusion criteria included age between 21 and 65, meeting Research Diagnostic Criteria for BD Type I, and

9 10 Bieling et al. experiencing at least the third discrete illness episode with a score of at least 15 on the HAM-D or a score of at least 15 on the Bech-Rafaelsen Mania Scale. Patients with rapid cycling, chronic drug or alcohol abuse and antisocial PD were excluded. Patients were assessed at each visit by independent evaluators blind to the participants classification. Only 3 of 12 (25%) BD and BPD (as assessed by the SCID-II) patients achieved stabilization while in the study compared with 43 of 58 (74%) BD- only patients. Two of the three BD- BPD patients who did stabilize took over 95 weeks to do so, compared with a median time to stabilization of 35 weeks in the BD-only group. The BD-BPD group also received significantly more atypical mood-stabilizing medications per year than the BD-only group. In addition, dropout rates in the comorbid group were high. As such, this study suggests that the treatment course may be longer in patients suffering from both BD Type I and BPD. The authors noted that some of the patients with comorbid illness improved substantially with pharmacotherapy and psychotherapy, suggesting that this approach is worthy of further investigation. Similar to the studies examining functional and psychosocial outcome, patients with BD and PD appear to respond less well to pharmacotherapy (see Table 1). BD patients who were being treated with lithium had larger number of relapses if there was a comorbid PD and those categorized as nonresponders tended to have higher neuroticism scores. Further, a higher proportion of BD patients who are non-compliant with medication tend to have Axis II comorbidity and patients with comorbity BD and PDs tend to drop out of treatment more often. One study found that although BPD dimensions improved significantly with treatment in both patient groups (with formal BPD and without), there was a trend for comorbid patients to require a second psychoactive medication during extended treatment. Finally, one study found that BD patients with PDs who achieved stabilization with medication take a significantly longer time to do so. Suicidality Suicide risk is elevated in BD (Dutta et al., 2007) and the role of comorbid PD has been examined in reference to history of suicide attempts. Leverich et al. (2003) investigated demographic and courseof-illness variables to better understand the incidence and potential clinical correlates of serious suicide attempts over an average of 2.8 years of follow-up in a subset of patients with BD (n = 648) followed through the Stanley Foundation Bipolar Network. A serious suicide attempt was defi ned as one requiring medical attention, emergency visit or hospitalization. Axis I diagnosis was based on the SCID and Axis II comorbidity was obtained from the self-rated Personality Diagnostic Questionnaire-4+. In total, 34% of patients had a history of suicide attempts. In a hierarchical cluster analysis, PDs from cluster B (antisocial, borderline, histrionic and narcissistic PDs) were a significant predictor of serious suicide attempt in addition to history of sexual abuse, lack of confidant prior to illness, hospitalizations for depression and suicidal thoughts when depressed. Further analyses suggested that PD comorbidity had an effect on suicidality above and beyond the effects of other comorbid psychiatric illness (e.g. anxiety disorder, substance abuse), loss of social supports, lack of health care access and negative life events. Garno, Goldberg, Ramirez, and Ritzler (2005) also examined the extent to which comorbid Cluster B (borderline, antisocial, histrionic and narcissistic) PDs impacted course and outcome for patients with BD and the risk of lifetime suicide attempts. Their sample consisted of 100 patients assessed in a BD research clinic. Seventy-three patients were diagnosed with BD Type I and 27 patients with BD Type II. Cluster B PDs were assessed using the SCID-II interview. Overall, 30% of patients met DSM-IV criteria for a Cluster B PD (17% borderline, 6% antisocial, 5% histrionic, 8% narcissistic). A suicide attempt was defi ned as a self-injurious or potentially self-injurious act associated with an acknowledged attempt to end one s life. Self-injurious behaviours that were not

10 Bipolar disorder and personality comorbidity 11 associated with intent to die (e.g. self-mutilation) were excluded in this study. Cluster B comorbidity was associated with significantly more lifetime suicide attempts and lifetime suicide attempts were significantly associated with cluster B comorbidity controlling for current depression severity, lifetime substance abuse and past sexual or emotional abuse. The authors state that their data indicate a strong link between cluster B comorbidity and lifetime suicidality in BD patients, and that this relation appears highly robust while controlling for current affective symptoms. Consistent with the previous two sections, these studies demonstrate that BD patients with comorbid PDs are likely to have an increased risk of suicidality compared to patients with BD alone (see Table 1). Specifically, the presence of a PD was a significant predictor of serious suicide attempt. Interesting to note was that Cluster B PD comorbidity in particular was significantly associated with more lifetime suicide attempts. Summary, recommendations and direction for future research In general, the data summarized in narrative form and displayed in Table 1 suggests that the presence of a PD exerts a broad and negative effect on outcome in BD. For instance, research shows that BD patients with a PD diagnosis are more likely to have had a past hospitalization, more likely to have a slow and possibly incomplete syndromic recovery, more likely to experience higher impaired functioning in occupational, residential, and social/leisure domains, and more likely to require psychosocial services than those without PD. The presence of PDs in patients with BD predicted poor adherence to prescribed medication, which may mediate the impact of PD on several of the outcome measures. With respect to suicidality, the presence of a PD is a significant predictor of serious suicide attempt in patients with BD and is associated with significantly more lifetime suicide attempts. While extant studies consistently suggest that comorbid PD exerts a negative effect on outcome in BD, the quality of methodologies employed in the relevant studies varies considerably. Most of the studies we located were naturalistic designs in which presence of PD was positively correlated with a dependent measure related to function. The number of participants per group was often small and time frames for follow-up were relatively short. Also, most of the research in this area is based on DSM-based defi nitions of Axis II disorders, and the extent to which these disorders are really distinct from Axis I disorders has certainly been challenged (see Bieling & MacQueen, 2005 for a review of the debate in this area). Furthermore, the use of DSM-defi ned PDs dismisses the impact that PD traits, even when sub-threshold for diagnosis, might exert on outcome. In most studies, patients who do not meet criteria for the DSM diagnosis of PD appear to be included in the no PD group, which may minimize the differences observed between the PD positive and the no PD groups. Few studies defi ne no PD as the absence of any or a few traits, which might be a more accurate representation of the outcome of people with very healthy personality functioning in spite of the diagnosis of BD. Directions for future research With respect to direction for future research, an ideal approach would include an opportunity to assess temperament/personality variables prior to the emergence of an Axis I illness, perhaps in those at risk for BD by virtue of an affected fi r st-deg ree relative. Moreover, a comprehensive and continuum-based measure of personality pathology is likely to be important to fully capture the relations between personality variables and outcome. The importance of large longitudinal studies of patients with BD has been recently recognized with a number of large-scale longitudinal studies of BD (Stanley Nework, STEP-BD). As such, these studies may provide the power to detect

11 12 Bieling et al. and evaluate relations between BD and PD and advance our understanding of the interrelatedness of these conditions and their impacts on patient outcomes. Evaluating for the presence of PD traits and including those as a grouping or stratification variable in randomized-controlled trials of either pharmacotherapy or psychotherapy would allow investigators to discern systematically the impact of such variables on efficacy of known or emerging treatment strategies. Clinical implications From a clinical perspective, our review leads to the following recommendations. First, given the impact of PDs on outcome and their frequency in BD, clinicians who assess for and treat BD must be comfortable with the assessment of PD. A structured assessment process, including, for example, a SCID-II interview or screen following Axis I assessment, is recommended, as is corroborating information from records or significant others. Documentation of the results of such a screen is important, in part for confi rming that a careful risk assessment has been completed. Second, because the presence of a PD appears to influence many aspects of treatment, including the development of a therapeutic alliance, adherence to treatment, type and efficacy of psychotherapy needed and efficacy of pharmacotherapy, the presence of PD comorbidity should be carefully considered in any prospective treatment plan. Adherence to mood stabilizing medication regimens particularly requires careful consideration and monitoring in comorbid patients, in part because not only can the presence of a PD interfere with adherence, but also because treatment response is likely to be less robust, at least initially, in this group. As the group with comorbid PD, particular BPD, is by defi nition more likely to be impulsive and engage in selfharm behaviours, particular consideration needs to be given to the lethality of medications prescribed to this group. Medications may need to be prescribed in smaller quantities and more regular monitoring by blood levels may be indicated. Finally, stabilization of Axis I symptoms should be followed expeditiously by considering adjunctive treatment for PD; ideally, this would include offering efficacious psychotherapy for PD (e.g. Dialetical Behaviour Therapy or Cognitive Analytic Therapy for BPD). This recommendation relies on the assumption that these treatments will remain efficacious for BPD despite the presence of the underlying Axis I disorder, and this is an assumption that urgently requires further empirical testing. Considered as a whole, the above strategies offer something of a treatment algorithm that could itself be tested empirically against usual care for patients with BD. References Abou-Saleh, M. T. (1983). Platelet MAO: Personality and response to lithium prophylaxis. Journal of Affective Disorders, 5, Akiskal, H. S., & Mallya, G. (1987). Criteria for the soft bipolar spectrum: Treatment implications. Psychopharmacology Bulletin, 23, Altman, E. G., Hedeker, D. R., Janicak, P. G., Peterson, J. L., & Davis, J. M. (1994). The clinician-administered rating scale for mania (CARS-M): Development of reliability and validity. Biological Psychiatry, 36, Bieling, P. J., & MacQueen, G. M. (2005). Bipolar disorder and personality: Constructs, fi ndings, and challenges. In M. Rosenbluth, S. H. Kennedy, & R. M. Bagby (Eds.), Depression and personality: Conceptual and clinical challenges (pp ). Washington, DC: American Psychiatric Publishing. Bieling, P. J., MacQueen, G. M., Marriot, M. J., Robb, J. C., Begin, H., Joffe, R. T., & Young, L. T. (2003). Longitudinal outcome in patients with bipolar disorder assessed by life-charting is influenced by DSM-IV personality disorder symptoms. Bipolar Disorder, 5, Colom, F., Vieta, E., Martinez-Aran, A., Reinares, M., Benabarre, A., & Gasto, C. (2000). Clinical factors associated with treatment noncompliance in euthymic bipolar patients. Journal of Clinical Psychiatry, 61, Dunayevich, E., Sax, K. W., Keck, P. E., McElroy, S. L., Sorter, M. T., McConville, B. J., & Strakowski, S. M. (2000). Twelve-month outcome in bipolar patients with and without personality disorders. Journal of Clinical Psychiatry, 61, Dunayevich, E., Strakowski, S. M., Sax, K. W., Sorter, M. T., Keck, P. E., McElroy, S. L., & McConville, B. (1996).

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