FIFTH INTERNATIONAL CONFERENCE 
ON BIPOLAR DISORDER

Poster Abstracts (151-175)

151. The Bipolar Treatment Optimization Program
S.V. Parikh, S.H. Kennedy
Centre for Addiction and Mental Health and University Health Network, Toronto, University Health Network, Toronto, Canada

Introduction: Difficulties in Bipolar Disorder (BD) treatment flow from incomplete understanding of the treatment needs of patients, insufficient training of treatment providers (particularly physicians) and the lack of integration of care. We developed a novel bipolar treatment optimization program (Bi-TOP) that provided time-limited ‘best-practices’ care to patients, in conjunction with an educational/health system intervention that taught such ‘best practices’ to physicians in a way that fostered ongoing collaboration and support and provided enhanced learning about BD. Our goals included preparing the physician to continue to treat the person with BD in a primary care setting.
Methods: This treatment program included an initial active phase of 3-6 months, followed by a low visit frequency maintenance phase. Outpatients with BD were recruited with only minimal exclusions. The community physician treating the individual was also entered. For the patients, we tailored interventions based on tertiary services already developed – medication optimization, specific psychoeducation, family interventions, and group supportive therapy. The physician intervention involved an assessment of learning needs, as ascertained by multiple questionnaires, followed by a carefully selected combination of existing CME programs on bipolar disorder and related mood disorders. Subjects were assessed monthly for mood symptoms, disability, relapses, social and occupational functioning, and medication use. Physician subjects were assessed for knowledge and skills gained, both during the educational intervention and 6 months later.
Results: 26 patients actively participated in the program. These participants showed statistically significant improvement in the SF-36, a significant decrease in scores for the HAMD-29, as well as a significant decrease in scores for the CARS-M at both the 6-month and 12-month follow-up visits. 19 physicians were enrolled in the program. Findings show that multiple barriers to treating bipolar patients were identified, including significant systems resource issues, educational issues on the part of the physicians, and public stigma.
Keywords: 1) Treatment Study 2) Health Services Research 3) Continuing Medical Education

152. Psycho-Education versus Cognitive-Behavioural Therapy for Bipolar Disorder
S.V. Parikh¹, A. Zaretsky¹, I. Patelis-Siotis², L. Yatham³, S. Beaulieu^4
1University of Toronto, Toronto, ²McMaster University, Hamilton, ³University of British Columbia, Vancouver, ⁴McGill University, Montreal, Canada

Introduction: Pharmacotherapy of bipolar disorder is necessary but not sufficient to adequately control episodes and prevent relapses. Adjunctive psychosocial interventions have demonstrated considerable promise, particularly psychoeducation and cognitive-behavioural therapy (CBT). Recent randomized controlled trials of both types of interventions have shown significant efficacy, and an earlier single site study we conducted comparing 7 sessions of psychoeducation to 20 sessions of CBT revealed few differences in outcome. In addition, the two treatments require different levels of intensity and cost, key issues when dealing with limited resources. In order to clarify the relative merits of each type of intervention, we are conducting a multisite randomized controlled trial comparing 6 sessions of group psychoeducation with 20 sessions of individual CBT.
Method: 210 adult subjects with Bipolar Disorder I or II, in partial or complete remission, are being recruited from 4 sites across Canada. Participants’ weekly illness burden and psychosocial functioning will be assessed longitudinally for 18 months on a monthly basis using a modified version of the Longitudinal Interval Follow-up Evaluation interview in addition to other secondary measures of symptom burden and functioning. Medication treatment is monitored, but will be done under naturalistic treatment conditions. Inclusion criteria are being kept particularly broad to ensure adequate generalizability.
Results: Study design, assessment issues, and recruitment difficulties will be discussed. In addition, initial results in terms of satisfaction with the intervention and retention in the study will be presented.
Keywords: 1) Treatment Study 2) Cognitive-behavior Therapy 3) Psycho-education

153. Quetiapine Monotherapy versus Placebo For Acute Bipolar Mania (STAMP 2)
B. Paulsson, K. Huizar
AstraZeneca, Södertälje, Sweden

Objective: Evaluate efficacy and safety of quetiapine monotherapy for acute mania.
Methods: 302 patients (bipolar I disorder, manic episode) were randomized to 12 weeks double-blind treatment with quetiapine (QTP) (up to 800 mg/d), placebo (PBO), or lithium (Li) (0.6 to 1.4 mEq/L target trough serum concentrations). Primary endpoint: change from baseline YMRS total score at Day 21 (QTP vs PBO; MITT, LOCF).
Results: 67.3% (72/107) of QTP-, 36.1% (35/97) PBO-, and 68.4% (67/98) Li-treated patients completed the trial. QTP-treated patients had a significantly greater reduction in mean YMRS scores vs. PBO at Day 21 (–14.62 vs. –6.71; P<0.0001), increasing by Day 84 (P<0.0001). Significantly more QTP patients achieved a response (>50% decrease from baseline YMRS score) at Day 21 (QTP 53.3%; PBO 27.4%; P=0.0002), and Day 84 (QTP 72%; PBO 41.1%; P<0.0001). There was also a statistically significant change in YMRS score for Li vs. PBO. QTP and Li were similar in all efficacy measures vs. PBO. Most common adverse events (>10%) in quetiapine-treated patients included dry mouth and somnolence. Lithium was associated with tremor and insomnia. Mean last-week QTP dose in responders at Day 21: 586 mg/d.
Conclusions: In acute mania, quetiapine monotherapy is well tolerated and significantly more effective than placebo.
Keywords: 1) Bipolar Disorder 2) Quetiapine 3) Mania

154. An Evidence-Based Pharmacotherapy Algorithm in Pediatric Bipolar Disorder
M.N. Pavuluri, D. Henry, J. Carbray, G. Sampson, M. Naylor, P.G. Janicak
University of Illinois at Chicago, Institute for Juvenile Research, Chicago, IL, USA

Objective: To assess the effectiveness of an evidence-based pharmacotherapy algorithm in the treatment of pediatric bipolar disorder (PBD).
Method: The study compared 64 Bipolar Type I subjects who were treated according to an algorithm developed in our specialty clinic (experimental group) to 31 Bipolar Type I subjects receiving standard care in a pharmacotherapy clinic (control group). Mean age of study sample was 11.74 years (SD=3.36 years). Subjects were diagnosed using the Washington University Schedule for Affective Disorders and Schizophrenia (WASH-U-KSADS), and scored an average of 26 (+ 4) on the YMRS. All subjects were assessed over an 18-month period using the CGI-BP severity scales and other measures.
Results: Pretest comparisons showed that the control group had a greater prevalence of Attention Deficit Hyperactivity Disorder (ADHD), Post Traumatic Stress Disorder (PTSD), Oppositional Defiant Disorder (ODD); switching with antidepressants/ stimulants; and delayed prescription of mood stabilizers. At pretest, the experimental group had a greater prevalence of elevated mood, grandiosity, psychotic features, and family history of bipolar disorder. Controlling for these differences and for pretest symptom severity, the experimental group showed significantly lower overall post-test severity on Clinical Global Impression Scale for Bipolar Disorder (CGI-BP) (1.8 + 1.2 vs. 3.4 +  0.9). At post-test, Clinical Global Assessment Scale (C-GAS) scores were above 60 in 37.9% of the experimental group, compared to none in the control group. 
Conclusion: An evidence-based problem-solving pharmacotherapy algorithm may be associated with better outcomes in the treatment of PBD. Randomized studies will be necessary to gather additional support for the algorithm’s effectiveness.
Keywords: 1) Pediatric Bipolar Disorder 2) Algorithm 3) Evidence-based

155. A Prospective Comparison of Risperidone versus Mood Stabilizers in Pediatric Bipolar Disorder
M.N. Pavuluri, D. Henry, J. Carbray, G. Sampson, M. Naylor, P.G. Janicak
University of Illinois at Chicago, Institute for Juvenile Research, Chicago, IL, USA

Introduction: This prospective, naturalistic study was conducted to compare the effects of mood stabilizers (lithium, divalproex sodium, carbamazapine), the second generation antipsychotic, risperidone, or their combination for symptoms of pediatric bipolar disorder (PBD).
Methods: Eighty-seven (87) outpatient children and adolescents with PBD and a mean age of 12.05 years (SD=3.23 years) diagnosed using the Washington University Kiddie Schedule for Affective Disorders and Schizophrenia, who scored a 15 or higher on the Young Mania Rating Scale were treated with mood stabilizer monotherapy, risperidone monotherapy or combination therapy. Progress was monitored prospectively using the Clinical Global Impression Scale for Bipolar Disorder (CGI-BP). Data was also collected on the Clinical Global Assessment Scale (C-GAS), frequency of cycling, hospitalizations, and medication adverse effects.
Results: Nine subjects were excluded because they did not receive adequate doses of the study medication. Random-effects regression models of CGI-BP on visits during the six month trial by medication group (risperidone only, n=20; mood stabilizers only, n=21; or combination, n=37), found improvement on all CGI-BP subscales was strong and significant regardless of medication group. Analysis of the predictors of medication choice showed that Attention Deficit Hyperactivity Disorder (ADHD) or a history of physical abuse resulted in a greater likelihood of receiving combination therapy. Risperidone monotherapy was associated with a more rapid improvement according to the CGI-BP Overall Improvement Scale. Combination therapy resulted in more rapid improvement on symptoms of depression, psychosis and sleep disturbance, according to their respective subscales.
Conclusion: Risperidone can be effective and safe in controlling the symptoms of PBD alone or in combination with standard mood stabilizers. Risperidone monotherapy may be effective for a subgroup of subjects who present with prominent irritability, whereas combination therapy may be more useful with patients who present with more severe symptoms (e.g., psychosis). It is also possible that risperidone may produce a more rapid onset of action.
Keywords: 1) Pediatric Bipolar Disorder 2) Risperidone 3) Mood Stabilizers

156. Improving Patient and Primary Care Understanding of Bipolar Variations
J.R. Phelps
Samaritan Mental Health, Corvallis, Oregon, USA

Introduction: Fifty-seven percent of those who looked for health information in the past 12 months consulted internet sources. Seventy-eight percent of U.S. physicians use the internet, and among those, two-thirds do so daily. Yet more than half of internet health information is unreferenced, vague or lacks information on who is speaking (Consumers International, April 2002). Meanwhile, the need for increased public understanding of complex bipolar variations such as hypomania and mixed states is apparent: few primary care doctors, or their patients, understand that bipolar disorder can occur without frank mania. The predominance of depression as the presenting form of bipolar II is not widely known. And critically, the risk of antidepressants for precipitating mania, mixed states and rapid cycling is similarly underappreciated.
Methods: Attempting to address this need, a website targeting local primary care physicians and established patients was developed (www.psycheducation.org). The site now offers extensive information on bipolar II, with hyperlinked references throughout. A resource center for primary care providers includes specific tools such as a downloadable Mood Disorders Questionnaire adapted for use in their offices, and step-by-step guidelines for prescribing first line mood stabilizers if they are unable to refer a patient directly to a psychiatrist.
Results: The site is now listed first on Google and MSN when searching “Bipolar II”. Hit rates are currently approximately 3000 home page and 5000 total visits per month. Interestingly, patient and family users outnumber physician use of the specific instructions on mood stabilizers (which come with warnings about use only under a physician’s direction) about 10:1. Feedback from users indicates some spread to other continents.
Keywords: 1) Education 2) Internet 3) Bipolar II

157. Separation Anxiety Symptoms in Patients with Bipolar Disorder
S. Pini, P. Iazzetta, M. Abelli, G.B. Cassano
Department of Psychiatry, University of Pisa, Pisa, Italy

Introduction: This study aimed to compare the frequency of childhood and adulthood separation anxiety symptom in patients with bipolar disorder or panic disorder and in a group of healthy controls.
Methods: Twenty four outpatients with panic disorder (PD), 23 with bipolar I disorder without comorbid panic disorder (BD), 14 with bipolar I disorder with comorbid panic disorder (BD+PD) and 15 healthy controls (CC) were recruited and assessed with the SCID-I, the Structured Clinical Interview for Separation Anxiety Symptoms (SCI-SAS), the Separation Anxiety Symptoms Inventory (SASI) and the Adult Separation Anxiety Checklist (ASA-CL).
Results: Mean age was 33.35±9.84 years for bipolar patients, 32.54±9.28 years for PD group and 27.13±5.99 years for CC group with no significant difference among groups. Females were respectively 20 (54.1%), 13 (54.2%) and 8 (53.3%) with no significant difference among groups. Regarding childhood separation anxiety, ANOVA post-hoc comparisons showed that patients with BD+PD had significant higher total scores than the PD group at SASI (significance level 0.010) and SCI-SAS (significance level 0.000). The BD group had higher score than PD group at SCI-SAS (significance level 0.025). As to adult separation anxiety, all clinical groups had significant higher scores than CC group. The BD+PD group had higher score than the BD, PD and CC groups. Linear regression analysis showed that adult separation anxiety was associated with earlier age at onset of bipolar disorder.
Conclusions: The present study suggests that childhood and adult separation anxiety symptoms are frequent in patient with bipolar disorder. Comorbidity between bipolar disorder and panic disorder is associated to greater severity of separation anxiety symptoms. Separation anxiety may warrant greater recognition as a specific psychopathological dimension in patient with bipolar disorder. Clinical implications of these data will be discussed.
Keywords: 1) Bipolar Disorder 2) Panic Disorder 3) Separation Anxiety

158. Retrospective Chart Review on the Use of Oxcarbazepine in Patients with Bipolar Disorder
D.E. Platt, F.A. Munasifi, L.M. McKay
Tallahassee Memorial Hospital, Tallahassee, FL, USA

Introduction: Oxcarbazepine is structurally related to the antiepileptic drug carbamazepine, a recognized therapeutic agent in the treatment of bipolar illness. Oxcarbazepine possesses similar efficacy as an antiepileptic drug, possibly mediated by some distinct mechanism of action and with an improved safety profile. Thus, oxcarbazepine may have antimanic or mood-stabilizing effects in patients with bipolar disorder.
Methods: A retrospective chart review of patients with bipolar disorder who received oxcarbazepine and had unsuccessful trials with numerous other agents, was conducted. Oxcarbazepine total daily dose ranged from 75 mg to 2400 mg/day as monotherapy or adjunctive therapy. The mood-stabilizing effects of oxcarbazepine were evaluated using Hamilton or Ziegler scores.
Results: Data from 146 charts were collected. The mean age was 33 years (range: 5-74) and mean final dose was 739 mg/day (range: 75-2400 mg/day). Forty-three patients received oxcarbazepine as monotherapy and 103 patients as adjunctive therapy. For the 88 patients for whom Hamilton scores were available, scores decreased from a pre-oxcarbazepine mean of 16.6 (range: 5-36) to a post-oxcarbazepine mean of 7.5 (range: 0-23). Ziegler scores were available for 46 patients and decreased from a pre-oxcarbazepine mean of 27.1 (range: 9-40) to a post-oxcarbazepine mean of 3.8 (range: 0-17). A total of 42 (29%) patients discontinued oxcarbazepine; 22 (14%) due to adverse events, 22 (14%) for inadequate response, and 2 (1%) for other reasons.
Conclusion: The data from this retrospective chart review suggest that oxcarbazepine may be useful in the treatment of bipolar disorder.
Keywords: 1) Oxcarbazepine 2) Treatment 3) Bipolar Affective Patients

159. Gender Differences in the Mood Patterns of Patients with Bipolar Disorder
N. Rasgon¹, M. Bauer², P. Grof³,  L. Gyulai⁴, T. Glenn⁵, P.C. Whybrow^6
1Department of Psychiatry, Stanford School of Medicine, Palo Alto, and Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles (UCLA), Los Angeles, CA, USA, ²Humboldt-University at Berlin, Charité University Hospital, Berlin, Germany and Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles (UCLA), Los Angeles, CA, USA, ³Department of Psychiatry, University of Ottawa, Royal Ottawa Hospital, Ottawa, Canada, ⁴Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, ⁵Tall Tree Software, Inc., Fullerton, CA, ⁶Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles (UCLA), Los Angeles, CA, USA

Introduction: The influence of gender on the mood patterns of patients with bipolar disorder (I or II) was studied.
Methods: For 3 months, 80 patients with bipolar disorder (35 men and 45 women) recorded mood, sleep, and medications daily using self-reporting software (ChronoRecord) on a home computer. Women also recorded menstrual data. 3483 days of data was received from men and 5179 days of data from women. Analyses were made using both the group data from all days and individual values.
Results: Over all days observed, men were depressed 15.9% of the time, normal 79.6%, and manic 4.5%; women were depressed 24.8%, normal 67% and manic 8.2%. Women reported severe symptoms of depression about twice as often as males (17.1% vs. 10.9%) and severe symptoms of mania about 5 times as often (18.7% vs. 3.2%). For both men and women, fluctuations in mood calculated for a difference of 1, 2, or 3 days that were greater than 10 in either direction on a 100-point scale occurred only 15% of the time. However more women than men (33.0% vs. 17.2%) experienced large mood fluctuations (greater than 20 on a 100-point scale). The majority of pre-menopausal women (65%) reported significant mood changes across the menstrual cycle.
Conclusions: Gender differences were observed in the mood patterns. Women were depressed more frequently and reported more severe symptoms of both depression and mania. Most mood changes reported by men and women were small; however women reported large mood changes about twice as often as men. Women also experienced mood changes across the menstrual cycle.
Keywords: 1) Gender 2) Mood Patterns 3) Menstrual Cycle

160. Characteristics of Responders in a Community-Based, Collaborative Randomized Clinical Trial of Cognitive Behavioral Group Therapy for Bipolar Disorder
R. Reiser, T.G. Shaffer, M. Basco, L.Thompson
Pacific Graduate School of Psychology, Palo Alto, CA, USA

This poster presents preliminary results from an ongoing randomized clinical trial designed to address the question of whether the addition of group Cognitive Behavioral Therapy (CBT) to Treatment-as-Usual (TAU) might improve outcomes in terms of stabilizing mood, reducing relapses, and improving functioning. At the present time 74 Bipolar I patients have been randomly assigned to group CBT or TAU. The manualized treatment program based on Basco & Rush (1996) is presented systematically over 16 weekly sessions followed by bimonthly and monthly maintenance sessions for up to one year. The goal is to assist clients in self-monitoring and self-management of their illness in order to reduce the number, length and intensity of future episodes. Since the study is still in progress, comparisons of treatment and control patients will be made elsewhere at the completion of the study. Preliminary results presented in this poster focus on individual differences between responders and non-responders to treatment as defined by change scores on the Hamilton Depression and Young Mania Rating Scales during the first 16 weeks of treatment. Ten patients were randomly selected from each category, and were administered a semi-structured interview that was designed to identify characteristics associated with increased stability of mood and improved functioning. The interview was designed to identify features of the treatment that appeared to be most helpful in sustaining improvements for responders. For non-responders, the interview attempted to identify common impediments to successful outcomes including homework compliance problems, the failure to actively practice and use skills that were newly acquired in therapy, as well as the potential impact of environmental factors (various negative life events during the course of therapy, including family conflicts, transportation, housing, and health-related problems).
Keywords: 1) Randomized 2) Bipolar 3) Community

161. Feasibility and Acceptance of a Randomized Clinical Trial of Cognitive Behavioral Group Therapy for Bipolar Disorder in a Community Mental Health Setting
R. Reiser, T.G. Shaffer, C. Sartor, S. Burns, L. Thompson
Pacific Graduate School of Psychology, Palo Alto, CA, USA

Implementing a randomized clinical trial for Bipolar Disorder utilizing evidence-based practices within a community mental health clinic setting presents significant challenges in terms of attracting, motivating and retaining seriously mentally ill clients in a structured treatment program. The initiative presented in this poster session involves a grant-funded collaboration between the Alliance For Community Care (ALLIANCE), a non-profit mental health services provider to over 4,000 seriously mentally ill clients in Santa Clara County, California, and the Pacific Graduate School of Psychology (PGSP).  The group-based intervention under study is a cognitive-behavioral therapy (CBT) approach designed to assist individuals in monitoring specific cognitive and behavioral changes that precede manic and depressive episodes and developing effective coping strategies. The manualized treatment program based on Basco & Rush (1996) is presented systematically over 16 weekly sessions followed by bimonthly and monthly maintenance sessions for up to one year. The goal is to assist clients in self-monitoring and self-management of their illness in order to reduce the number, length and intensity of future episodes.  An initial survey of client satisfaction indicates a high level of acceptance and satisfaction with the group-based treatment program. For example, 100% of clients reported that their goals had been met by the treatment program; and, 88% of clients reported that the intervention was “extremely effective” in helping them with their problems. This poster will present additional data from focus groups including specific client feedback evaluating components of the cognitive behavioral intervention that appeared to be most effective as well as addressing future enhancements to increase the effectiveness of the manualized intervention and client workbook.
Keywords: 1) Randomized 2) Bipolar 3) Community

162. Systematic Review of Olanzapine Alone or in Combination for Acute Mania
J.M. Rendell, H.J. Gijsman, P. Keck, G.M. Goodwin, J.R. Geddes
Department of Psychiatry, University of Oxford, Oxford, UK

Introduction:  The review assessed evidence for the efficacy, acceptability and adverse effects of olanzapine in the treatment of mania in comparison with placebo or other drug treatment. A search of electronic databases and Cochrane trial registers identified 7 randomized controlled trials (1467 participants) comparing olanzapine with placebo (as monotherapy or adjunctive treatment), divalproex, lithium, lamotrigine or haloperidol.
Results: Interpretation of the results was hindered by high rates of failure to complete trial treatment (29%-65%). Olanzapine improved manic symptoms scores more than placebo both as monotherapy (fixed effects WMD: -5.94, 95% CI -9.09 to -2.80) and as adjunctive treatment to lithium or divalproex (WMD: -4.01, 95% CI -6.06 to -1.96). Olanzapine was superior to divalproex (fixed effects SMD: -0.29, 95% CI -0.50 to -0.08). No difference was found between olanzapine and haloperidol in response rates. Reduction of psychotic symptoms (where present) and overall illness severity illness was greater for olanzapine than placebo (PANNS fixed effects WMD –7.42 95% CI –10.33 to –4.50) and (CGI fixed effects –0.42 95% CI –0.64 to –0.20). Evidence for effect on depression was less clear. Olanzapine monotherapy was associated with a lower rate of failure to complete treatment than placebo (fixed effects RR: 0.62, 95% CI 0.48 to 0.80) but similar rates to divalproex, lithium, lamotrigine and haloperidol. Olanzapine caused more movement disorders than divalproex but fewer than haloperidol. Olanzapine caused greater weight gain than divalproex or haloperidol.
Conclusion: Olanzapine is an effective treatment for mania which may be superior to divalproex and comparable to haloperidol. Acceptability of olanzapine was comparable to that of divalproex and haloperidol. The different adverse effect profiles of specific medications should be considered in choice of treatment for mania.
Keywords: 1) Olanzapine 2) Mania 3) Review

163. Extrapyramidal Symptoms with Atypical Neuroleptics in Bipolar Disorder
K.J. Rosenquist¹, D.J. Hsu¹, F. K. Goodwin², S.N. Ghaemi^1
1The Cambridge Hospital, Cambridge, MA, Harvard Medical School, Boston, MA, ²George Washington University, School of Medicine, Washington, DC, USA

Introduction: To examine, in a real-world clinical setting, the risk of extrapyramidal symptoms (EPS) with atypical neuroleptics in patients with bipolar disorder.
Methods: We assessed results of 27 atypical trials (9 risperidone, 9 quetiapine, 6 ziprasidone, 3 olanzapine) in 20 patients with Bipolar Disorder Type I. Risk of EPS was assessed using the Abnormal Involuntary Movement Scale, Barnes Akathisia Rating Scale, and the Simpson-Angus Scale. Median duration of treatment was 18 weeks (range 5-94 weeks) and 74% of patients were female.
Results: 48.1% of trials resulted in EPS. Frequency of EPS and frequency of discontinuation did not differ statistically between specific neuroleptic agents or between high potency (risperidone/ziprasidone; 8/15 trials, 53.3%) and low potency (quetiapine/olanzapine; 5/12 trials, 41.7%) agents. 22.2% of trials were discontinued due to side effects, including three trials in two patients that were discontinued due to tardive dyskinesia.
Conclusions: About one-half of patients experienced EPS in this real-world clinical setting. This rate is much higher than the 5-15% range reported in clinical trials, suggesting problems with clinical trial generalizability. The apparent tardive dyskinesia rate in our sample was about 7%, which is higher than expected from studies of schizophrenia, and may require further investigation in bipolar disorder. These data will be updated before presentation.
Keywords: 1) Akathisia 2) Extrapyramidal Symptoms 3) Atypical Neuroleptics

164. The Mood Spectrum in Unipolar and Bipolar Patients
P. Rucci, G.B. Cassano, E. Frank, A. Fagiolini, L. Dell’Osso, M.K. Shear, D.J. Kupfer
University of Pittsburgh School of Medicine, Pittsburgh, PA

Introduction: To examine the extent to which individuals with a clear-cut lifetime diagnosis of recurrent unipolar disorder endorse experiencing manic-hypomanic symptoms over their lifetime and to compare their reports with those of patients with bipolar I disorder.
Method: The study sample includes 117 patients with recurrent unipolar depression (MDDRU) in remission and 106 patients with bipolar I disorder (BP). Subjects had their clinical diagnosis confirmed by MINI International Neuropsychiatric Interview and then were administered the Structured Clinical Interview for the Mood Spectrum, which assesses the lifetime symptoms, traits and lifestyles that characterize threshold and sub-threshold mood episodes as well as ‘temperamental’ features related to mood dysregulation. Results: The MDDRU patients endorsed experiencing a substantial number of manic-hypomanic spectrum symptoms over their lifetime. Both in MDDRU and in BP patients, the number of manic-hypomanic spectrum items endorsed was related to the number of depressive spectrum items endorsed. In the MDDRU group, the number of manic-hypomanic spectrum items was related to an increased likelihood of endorsing paranoid and delusional thoughts and suicidal ideation. In the BP group, the number of lifetime manic-hypomanic spectrum items was related to suicidal ideation and just one indicator of psychosis.
Conclusions: The presence of a significant number of manic-hypomanic items in MDDRU patients seems to challenge the traditional dichotomy unipolar-bipolar disorder and bridge the gap between these two categories of mood disorders. We argue that our Mood Spectrum approach is useful for a more accurate diagnostic evaluation and to inform treatment decisions in mood disorder patients.
Keywords: 1) Bipolar Spectrum 2) Mood Spectrum 3) Hypomanic Symptoms in Recurrent Unipolar Depression

165. Mindshifting: A Family’s Call for Action
N. L. Rutter
Rutter Communications, Des Moines, IA, USA

Both my husband and 11-year-old son were recently diagnosed with bipolar disorder by PET (Positron Emission Tomography) scans. My son, we are told, also has ADHD. These diagnoses came after years of misdiagnosis and countless medication trials. Our family’s health journey has been arduous, costly, and painful. It has also been enlightening. Our experiences highlight the need for a major health care paradigm change. I call it mindshifting. The current model separates “mental” from “physical” disorders. This model is invalid and must be replaced. It promotes a singular focus on brain chemistry for conditions such as bipolar disorder. There is often little or no support for nutritional analysis, educational needs assessment, consideration of such cognitive options as neurofeedback, or approaches designed to renew the spirit. Mental health care practitioners are not encouraged to link assessments and resources with other health care practitioners. An integrated, holistic approach promises a more complete and long-term solution for people like my husband and son. Consider, for example, nutrition and its relationship to bipolar disorder. Processed foods are often stripped of nutrients, so many of us are nutrient deficient. Bipolar disorder is thought to affect less than 2% of the population, yet interest in the condition is exploding. Is there a connection? What if nutrient deficient diets create more vulnerability for those who carry a genetic predisposition to bipolar disorder? Omega 3 may be the first of several dietary linkages. Many have already embraced the mind, body, spirit connection, but there is much work to be done. On behalf of consumers and their families, I call on researchers, physicians, educators, legislators, insurers and other influential people to advocate for funding research and developing solutions that treat our loved ones holistically. Our goal must be prevention and wellness, rather than crisis management. We need radical mindshifting.
Keywords: 1) Family 2) Mindshifting 3) Holistic

166. Clinical Presentation of Bipolar Patients with and without Co-Morbid Diabetes Mellitus
M. Ruzickova, C. Slaney, J. Garnham, M. Alda
Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada

Introduction: The risk of diabetes mellitus (DM) in bipolar disorder (BD) has been reported to be about 3 times higher than in the general population. There may be multiple reasons for the co morbidity, including life style, treatment effects, hormonal changes, and/or changes at the signal transduction level, possibly on a genetic basis. As a starting point in investigating the relationship between the two disorders, we carried out a study comparing the clinical picture between bipolar subjects with and without DM.
Method: We examined the clinical data of diabetic and non-diabetic subjects from The Maritime Bipolar Registry. The total sample of 222 consisted of 86 males and 136 females in the age range of 15 to 82 years, diagnosed with bipolar I (n=151), bipolar II (n=65), or bipolar NOS (n=6) disorders. Their data included details of clinical presentation such as course of illness, rapid cycling, history of psychotic symptoms, suicidal behavior, co morbidity, type of treatment, GAF, hypertension, and thyroid disorder. We first analyzed the data using chi-square for categorical, and Wilcoxon test for continuous variables. The variables showing differences between the groups were then analyzed using logistic regression with DM as a dependent variable.
Results: The prevalence of DM in the sample was 11.7% (n=26). The mean age of subjects with diabetes was higher than that of non-diabetics (p=0.0001). The diabetic group showed significantly higher rates of rapid cycling (p=0.017), high blood pressure (p=0.003), and worse outcome on GAF (p=0.009). Non-diabetic subjects had higher prevalence of episodic course of BD (p=0.006). Lifetime history of antipsychotic treatment was associated with an insignificant elevation of the risk (p=0.16).
Conclusions: Presence of co-morbid diabetes in patients with bipolar disorder has relevance for their prognosis, and outcome.
Keywords: 1) Bipolar Disorder 2) Diabetes Mellitus 3) Clinical Presentation

167. Brain Derived Neurotrophic Factor Gene Polymorphism and Prefrontal Function in Bipolar Patients
J.K. Rybakowski¹, A.Borkowska², P.M.Czerski¹, M.Skibinska¹, J.Hauser^1
1University of Medical Sciences, Poznan, ²University Medical School, Bydgoszcz, Poland

Introduction: Brain-derived neurotrophic factor (BDNF) has been shown a potent modulator of synaptic transmission and plasticity in central nervous system and has been implicated in such cognitive processes as memory and learning. Recent investigations have demonstrated an association between BDNF gene polymorphism and bipolar affective illness. The aim of the study was to test a possible association between the Val66Met polymorphism of BDNF gene and performance on a cognitive test of prefrontal function, the Wisconsin Card Sorting Test (WCST), in bipolar patients.
Methods: Fifty four bipolar patients were studied, 18 male, 36 female, aged 18-72 (mean 46 years). The number of perseverative errors (WCST - P), non-perseverative errors (WCST-NP), completed corrected categories (WCST – CC), conceptual level responses (WCST-%CONC) and set to the first category (WCST-1st CAT) were measured in relation to the Val66Met genotypes of BDNF.
Results: The percentages of subjects with Val/Val, Val/Met and Met/Met genotypes were respectively 81.5%, 16.7% and 1.8%. Subjects with Val/Val (n=44) and Val/Met (n=9) genotypes did not differ on clinical factors. The performance in all domains of WCST was significantly better in subjects with Val/Val BDNF genotype compared with Val/Met genotype.
Conclusions: The results suggest a role of BDNF in prefrontal cognitive function in bipolar illness. The tests of prefrontal cognition may be considered as endophenotypic markers in bipolar illness.
Keywords: 1) Bipolar Disorder 2) Brain-derived Neurotrophic Factor 3) Wisconsin Card Sorting Test

168. The Frequency of Bipolar Mood Disorder among Polish Psychiatric Depressive Outpatients
J.K.Rybakowski¹, A.Kiejna^2
1University of Medical Sciences, Poznan, ²University Medical School, Wroclaw, Poland

Introduction: Recent studies have shown that in a significant proportion of patients treated for depression there are various types of bipolar affective illness. The aim of the study was to assess possible diagnostic categories of bipolar mood disorder among depressive patients treated in outpatient settings by psychiatrists in Poland.
Methods: Ninety-six psychiatrists throughout the country participated in the study, and 880 patients having at least one major depressive episode were assessed. Bipolar I category was diagnosed on the basis of a history of manic or mixed state, bipolar II on the basis of hypomanic state and bipolar spectrum disorder according to the criteria of Mood Disorder Questionnaire (Hirschfeld et al., 2000) and/or diagnostic criteria for bipolar spectrum disorder proposed by Ghaemi et al (2001).
Results: About sixty percent of patients studied belonged to some category of bipolar mood disorder. Bipolar I disorder was more frequently diagnosed in male than in female patients (27.4% vs. 17.6%) and bipolar II disorder was more often recognized in female than in male patients (31.7% vs. 21.5%). The criteria for bipolar spectrum disorder were met by 12% of patients studied. Patients with age ranges 19-49 and 50-65 years did not differ as to the percentage of diagnostic categories. Compared with subjects diagnosed as unipolar mood disorder (single or recurrent depressive episode), bipolar patients had significantly earlier onset of the illness and displayed significantly more frequently symptoms of atypical depression, psychotic depression and postpartum depression in females.
Conclusions: The results obtained indicate that bipolar mood disorder is very prevalent among depressive outpatients treated by psychiatrists in Poland. About 1/5 of bipolar patients may belong to bipolar spectrum disorder category.
Keywords: 1) Bipolar Mood Disorder 2) Bipolar Spectrum Disorder 3) Epidemiology

169. Effects of Lithium and Lamotrigine Prophylaxis Therapy on Body Weight in Patients with Bipolar I Disorder
G. Sachs¹, A.H. Young², L. Ginsberg³, J. Calabrese⁴, C. Bowden⁵, Z. Antonijevic^6
1Bipolar Treatment Center, Harvard University, Boston, MA, USA, ²University of Newcastle, Newcastle upon Tyne, UK, ³Red Oak Psychiatry Associates, Houston, TX, USA, ⁴Case Western Reserve University, Cleveland, OH, USA, ⁵Health Science Center at San Antonio, University of Texas, San Antonio, TX, USA, ⁶GlaxoSmithKline, Research Triangle Park, NC, USA

Introduction: Weight gain, a common outcome of treatment for bipolar disorder, has been associated with various treatments as well as a history of obesity. We examined the effects of two mood stabilizers, lithium and lamotrigine, on body weight for patients with and without a pretreatment history of obesity.
Methods: 638 patients randomized to 18 months of double-blind monotherapy with lamotrigine (n=280; 50-400mg/day fixed and flexible dose), lithium (n=167; 0.8-1.1mEq) or placebo (n=191) were grouped by pretreatment body mass index (BMI): not obese = BMI < 30, obese = BMI > 30. Mean observed change in body weight was examined through 52 weeks of treatment. Random effects mixed model with subject as a random effect and treatment, BMI category, visit, BMI category by visit interaction, and treatment by visit interaction as fixed effects was performed.
Results: After 52 weeks of treatment, mean change in body weight was significantly smaller in the lamotrigine treatment group compared with placebo (p< 0.011) and compared with lithium (p<0.0001). These differences were evident in both BMI categories, but were most evident in the obese category of patients: placebo + 1.46 kg, lithium +3.3 kg, and lamotrigine -2.96 kg. Conclusions: Changes in body weight were associated with choice of mood stabilizer and pretreatment history of obesity. Patients categorized as obese were at greatest risk for weight gain with lithium. Weight gain was not a complicating factor for lamotrigine treatment in the long term management of bipolar I disorder.
Keywords: 1) Lamotrigine 2) Bipolar Depression 3) Efficacy

170. Florida Medicaid Costs of Atypical Antipsychotics in Bipolar Disorder
K. Sadik¹, A. Grogg¹, A. McDermott², J. Malkin^3
1Janssen Pharmaceutica, Titusville, NJ, ²Covance Health Economics and Outcomes Services Inc., Gaithersburg, MD, ³RAND Corporation, Arlington, VA, USA

Introduction: Using Florida Medicaid claims, we evaluated the association between atypical antipsychotic therapies and payer costs among nonelderly bipolar patients.
Methods: Patients who received risperidone (n=113) or olanzapine (n=131) in the first half of 1998 and no other atypical antipsychotics the year before were included. The primary outcome was change in total payer costs from 1 year before to 1 year after study therapy initiation. Secondary outcomes included differences in mental health inpatient, outpatient, and medication costs. Each outcome was modeled (median regression with bootstrapping) as a function of study therapy, demographics, mental health comorbidities, and prior inpatient stays and duration of conventional therapy.
Results: Total costs decreased an average of $857 after risperidone initiation and increased $2,667 after olanzapine initiation (p=0.003). After controlling for all other variables, olanzapine was associated with significantly greater increases in total costs, with an adjusted median difference between treatments of $2,256 (p=0.002). Differences in mental health medication costs were marginally greater for olanzapine ($523; p=0.092).
Conclusion: Risperidone was associated with reduced total costs, whereas olanzapine was associated with increased total costs among Medicaid patients with bipolar disorder. Importance: Rising healthcare costs dictate careful consideration of therapy choices.
Keywords: 1) Risperidone 2) Olanzapine 3) Treatment Costs

171. Combined Naltrexone Valproate in Bipolar Alcoholics: A Randomized, Open-label, Pilot Study
I.M. Salloum, J.R. Cornelius, S. Chakravorthy
University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

Introduction: The combined pharmacotherapy of valproate, an antikindling agent approved for the treatment of bipolar disorder, and found useful in the management of alcohol and other drug withdrawal states, and naltrexone, an opiate antagonist that blocks the positive reinforcing effects of alcohol, may be particularly useful in bipolar disorder with comorbid alcohol dependence. We conducted an open-label, randomized, pilot study of 8 weeks duration to examine the utility of combined pharmacotherapy of valproate (target serum levels 50 to 110 µg/ml) + naltrexone (50 mg/daily) (Nal+Val) vs. valproate alone (Val) in decreasing alcohol use in patients with bipolar disorder and comorbid alcohol dependence and other substance use disorders.
Methods: Adult, males and females,18-65 years of age, who met the study inclusion criteria (confirmed by the DSM-IV/SCID) were randomized to treatment groups, and assessed using the Addiction Severity Index, the Timeline Followback for Assessing Recent Drinking, the Hamilton Rating Scale for Depression, the Bech-Rafaelsen Mania Scale, The Obsessive Compulsive Drinking Scale, the Pittsburgh Sleep Quality Index, the Global Assessment Scale, and the Somatic Symptoms checklist to assess medication side effects. Eight subjects (four in each group) took their assigned medication for at least one week and were included in the analyses. Results: The results indicated that none of the Nal+Val group relapsed to alcohol use during the 8-week trial, while 75% of the Val only group did relapse. The Nal+Val group had better outcome on depression (m=7.0, sd=8.0 vs. m=18.5, sd=11.2), mania (m=0.75, sd=0.95 vs. m=3.0, sd=1.4), alcohol craving (mean=5.2, sd=5.73 vs. m=20.25 ,sd=14.61), sleep difficulties (m=3.75 ,sd=2.21 vs. m=9.33 ,sd=4.93), functioning (m=68.75, sd=11.35 vs. m=56.25, sd=10.30), and reported medication side effects (m=2.0, sd=2.7 vs. m=7.25, sd=4.27). The combination medication was well tolerated by all subjects. Liver function tests were within normal limits for both groups although the combined medication group had slightly higher levels. These results support the utility of combined naltrexone + valproate in bipolar alcoholics. Double-blind clinical trials are warranted since most or all of these results may be due to the small sample size, the lack of blind condition, and to the lack of placebo arm.
Acknowledgements:  Supported by a VA VISN4 MIRECC, and in part by R29 AA10523, R01 AA11929, and R01 AA13370 grants.
Keywords: 1) Comorbid Bipolar Alcoholics 2) Naltrexone 3) Combined Pharmacotherpy

172. Efficacy of Valproate in Bipolar Alcoholics: A Double Blind, Placebo-controlled Study
I.M. Salloum, J.R. Cornelius, D.C. Daley, L. Kirisci, J. Himmelhoch, M.E. Thase
University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

Introduction: Comorbid alcohol and other substance use disorders are highly prevalent in bipolar disorder. There are no treatments specifically targeting this high-risk comorbid condition. We conducted a double blind, placebo-controlled study to evaluated the efficacy of valproate maintenance in decreasing alcohol use and stabilizing mood symptoms in actively drinking, acutely ill bipolar alcoholics.
Methods: Fifty-two patients with DSM-IV/SCID comorbid diagnoses of bipolar I disorder and alcohol dependence were randomized to two treatment groups: Valproate + Treatment-as-Usual (TAU) (TAU included lithium carbonate) versus placebo + TAU. Subjects were examined every two weeks for a 24-week period using the Timeline Followback for Recent Drinking, the Hamilton Rating Scale for Depression (HAM-25) and the Bech-Rafaelsen Mania Scale. Liver functions tests (AST, ALT, and GTP) were obtained on baseline, and on weeks 2, 4, 8, 12, 16, 20, and 24. The Mixed Model with restricted maximum likelihood estimation method and unrestricted covariance matrix was used to analyze longitudinal data. First we used the mixed model with following covariates: time of assessment, bipolar subtype (mixed, manic, depressed), and treatment group (placebo, valproate). The second nested model included an additional covariate of compliance.
Results: The results revealed that the valproate group had significantly fewer proportion of heavy drinking days (P<0.03) and fewer number of drinks per heavy drinking day (p=0.055) than the placebo group. When compliance was entered in the model, subjects in the valproate group had significantly fewer proportion of heavy drinking days (P<0.04), fewer number of drinks per heavy drinking day (p<0.02), and fewer number of drinks per drinking day (p <0.03). There was a trend towards significance in reporting lower proportion of any drinking days (p=0.08). Valproate and the placebo group did not differ on improvement in manic or depressive symptoms. Furthermore, valproate was well tolerated and did not significantly alter liver function tests compared to the placebo group.
Acknowledgements:  Supported by R29 AA10523, and in part by R01 AA11929, R01AA13370, and a VA MIRECC grants.
Keywords: 1) Valproate 2) Bipolar Alcoholics 3) Treatment

173. The Subgenual Prefrontal Cortex of Adolescent Bipolar Patients: A Morphometric MRI Study
M. Sanches^1,2,3, R.B. Sassi⁴, D. Axelson⁵, M. Nicoletti^1,2, P. Brambilla⁶, J.P. Hatch¹, M.S. Keshavan³, N. Ryan⁵, B. Birmaher⁵, J.C. Soares^1,2
1Division of Mood and Anxiety Disorders, Department of Psychiatry, The University of Texas Health Science Center at San Antonio, San Antonio, TX, ²South Texas Veterans Health Care System, Audie L. Murphy Division, San Antonio, TX, ³Department of Psychiatry, Federal University of Sao Paulo, Sao Paulo, Brazil, ⁴Department of Psychiatry, University of Sao Paulo School of Medicine, Sao Paulo, Brazil, ⁵Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, PA, USA, ⁶Department of Psychiatry, IRCSS S. Matteo, University of Pavia School of Medicine, Italy

Introduction: Anatomical abnormalities in brain structures of adolescents with mood disorders have been reported, and suggest that neurodevelopmental abnormalities may be involved in illness pathophysiology. The subgenual prefrontal cortex (SGPFC) corresponds to the Broadman area 24 and has been regarded as a site that plays an important role in emotional processing. We carried out a MRI study of the volume of the SGPFC in adolescent bipolar patients (BP) and healthy controls (HC).
Methods: The sample consisted of 16 adolescents who met DSM-IV criteria for bipolar disorder (mean age + S.D.= 15.5 + 3.4 years) and 21 healthy adolescents (mean age + S.D.= 16.9 + 3.8 years). MRI images were obtained with a 1.5 T GE Signa Imaging System with Signa 5.4.3 software. SGPFC volumes were measured with the semi-automated software MedX (Sensor Systems, Sterling, VA, USA), by a trained evaluator, blind to subjects’ diagnosis.
Results: The volumes (mean + S.D.) of the right and left SGPFC for BP were 291.27 + 88.70 mm³ and 284.86 + 83.98 mm³ , respectively. For HC, the right and left SGPRC values were 284.95 + 73.33 mm³ and 307.55 + 73.67 mm³ (left SGPFC), respectively. ANCOVA was performed to compare SGPFC volumes between BP and HC, with age, gender and ICV as covariates. There were no statistically significant differences between groups regarding right (F=0.35, d.f.=1/32, p=0.56) or left SGPFC (F=0.14, d.f.=1/32, p=0.71).
Conclusion: We found no evidence of volumetric abnormalities in SGPFC in bipolar adolescents. However, most patients in our sample had been medicated with a mood stabilizer. Future studies, using larger samples of untreated subjects and a longitudinal design will be necessary.
Acknowledgements:  This work was supported by grants MH 01736, MH 55123, MH 30915, and MH 59929 from the National Institute of Mental Health, NARSAD and CAPES Foundation (Brazil).
Keywords: 1) Neuroimaging 2) Prefrontal Cortex 3) MRI

174. Aripiprazole vs. Haloperidol for Maintained Treatment Effect in Acute Mania
R. Sanchez¹, M. Bourin², P. Auby³, R. Swanik³, R. Marcus¹, R.D. McQuade⁴, T. Iwamoto³, E. Stock^1
1Bristol-Myers Squibb, Wallingford, Connecticut, USA, ²EA 3256 Neurobiologie de l'Anxiété et de la Dépression, Faculté de Médecine, Nantes, France, ³Bristol-Myers Squibb, Waterloo, Belgium, ⁴Bristol-Myers Squibb, Lawrenceville, Princeton, NJ, USA

Objective: To compare the number of aripiprazole-treated patients with haloperidol-treated patients who continued on treatment and maintained response after 12 weeks of treatment of an acute manic episode.
Methods: This 12-week, multicenter, double-blind study randomized 347 in- and out-patients with acute manic or mixed episodes, to either aripiprazole 15 mg/day or haloperidol 10 mg/day. Doses could be titrated in Weeks 1–3 to improve response and/or tolerability (aripiprazole 15–30 mg, haloperidol 10–15 mg). The primary efficacy measure was response at Week 12, defined as ≥50% improvement from baseline in Young Mania Rating Scale (Y-MRS) score, and continuation of therapy.
Results: At Week 12, significantly more patients responded and remained on aripiprazole (50%) than on haloperidol (28%; p<0.001). There were marked differences in long-term continuation rates for the two treatments (29.1% of patients remained on haloperidol compared with 50.9% on aripiprazole). The major reason for discontinuation in the haloperidol group was adverse events. Extrapyramidal Syndrome was reported in 36% of haloperidol patients versus 9% with aripiprazole. Neither drug was associated with weight gain during the study period.
Conclusion: Aripiprazole treatment led to significantly higher response rates and improved tolerability over haloperidol for maintained treatment effect in acute mania at 12 weeks.
Keywords: 1) Aripiprazole 2) Antipsychotic 3) Acute Mania

175. The Inventory of Depressive Symptomatology – German Translation and Validation of Self-rated Assessment in a Sample of Bipolar and Unipolar Patients
L.O. Schaerer, Y. Graesslin, N.C. Biedermann, S. Walser, G. Valerius, C. Born, M.C. Strobl, S. Frey, V. Hartweg, M. Graf, M. Hoern, J. Walden, J.M. Langosch
University Hospital for Psychiatry and Psychotherapy, Freiburg, Germany

Introduction: The Inventory of Depressive Symptomatology (IDS) developed by Rush et al. in 1986 is a new and powerful diagnostic tool for depression. Two matched versions were developed for clinician-rated and self-reported use. The 30 items of these two corresponding versions were chosen under consideration of current diagnostic criteria and in an interactive process between clinical experts and patients.
Methods: The self-reported version of Inventory of Depressive Symptomatology (IDS-SR) was translated into German. In a sample of 75 ratings, the IDS-SR and the Beck Depression Inventory (BDI) were administered to unipolar and bipolar in- and outpatients. Additionally, the formerly translated clinician-rated version of the Inventory of Depressive Symptomatology (IDS-C) and the Hamilton Rating Scale for Depression (Ham-D) were completed by clinical raters.
Results: The German version of IDS-SR had good internal consistence (Cronbach´s Alpha = 0,92).Validity was examined by comparison with the BDI and the Ham-D. Factorial and discriminantal analyses were done. Good concurrent validity was given by significant correlations between IDS-SR and BDI (r = 0,93; p < 0,01) as well as between IDS-SR and Ham-D (r = 0,90; p < 0,01). IDS-SR was highly correlated with IDS-C (r = 0,91; p < 0,01) and showed similar factorial and discriminant structures. The German version of IDS-SR seems to be applicable for unipolar as well as for bipolar patients and appears to be useful in ambulant and clinical settings. The IDS-SR might be a good alternative to the clinician rated version, especially when frequent ratings in long-term observations are needed.
Keywords: 1) Inventory of Depressive Symptomatology 2) Self-rating 3) Bipolar disorder