Anthony J. Levitt

Anxious and non-anxious bipolar disorder

Eighty-one outpatients with bipolar disorder (BD) were grouped by SADS anxiety symptom scores (high vs. low) or diagnosis of generalized anxiety disorder, and/or panic disorder. BD patients with high anxiety scores were more likely to have suicidal behaviour (44% vs. 19%), alcohol abuse (28% vs. 6%), cyclothymia (44% vs. 21%) and an anxiety disorder (56% vs. 25%) with a trend toward lithium non-responsiveness. Diagnosis of an anxiety disorder was related only to high anxiety and lower GAS scores. Thus, anxiety may have similar clinical relevance in BD as it does in unipolar patients.

A comparison of Tridimensional Personality Questionnaire dimensions in bipolar disorder and unipolar depression

The harm avoidance (HA) personality dimension has been hypothesized to be a vulnerability factor for unipolar depression (UD) but not for bipolar disorder (BD). The reported difference on HA scores between these diagnostic groups may have been compromised by the assessment of BD patients who had not fully recovered. To test the diagnostic specificity of elevated HA scores and to elucidate whether assumptions about differences between patients with UD or BD might be attributed to the lingering effects of mood state, the Tridimensional Personality Questionnaire (TPQ) was administered to recovered patients with either BD or UD and a nonpatient comparison group. Both patient groups scored higher on the HA dimension than the nonpatient comparison group, but the patient groups did not differ from one another on this dimension. Moreover, novelty seeking (NS) scores were elevated in subjects with BD compared with both UD patients and nonpatient subjects. These results suggest that high HA scores may be associated with a mood disorder diagnosis, whereas high NS scores may be associated with the BD subtype.

Does inclusion of a placebo arm influence response to active antidepressant treatment in randomized controlled trials? Results from pooled and meta-analyses.

OBJECTIVE To determine if the inclusion of a placebo arm and/or the number of active comparators in antidepressant trials influences the response rates of the active medication and/or placebo. DATA SOURCES Searches of MEDLINE, PsycINFO, and pharmaceutical Web sites for published trials or trials conducted but unpublished between January 1996 and October 2007. STUDY SELECTION 2,275 citations were reviewed, 285 studies were retrieved, and 90 were included in the analysis. Trials reporting response and/or remission rates in adult subjects treated with an antidepressant monotherapy for unipolar major depression were included. DATA EXTRACTION The primary investigator recorded the number of responders and/or remitters in the intent-to-treat population of each study arm or computed these numbers using the quoted rates. DATA SYNTHESIS Poisson regression analyses demonstrated that mean response rate for the active medication was higher in studies comparing 2 or more active medications without a placebo arm than in studies comparing 2 or more active medications with a placebo arm (65.4% vs 57.7%, P < .0001) or in studies comparing only 1 active medication with placebo (65.4% vs 51.7%, P = .0005). Mean response rate for placebo was significantly lower in studies comparing 1 rather than 2 or more active medications (34.3% vs 44.6%, P = .003). Mean remission rates followed a similar pattern. Meta-analysis confirmed results from the pooled analysis. CONCLUSIONS These data suggest that antidepressant response rates in randomized control trials may be influenced by the presence of a placebo arm and by the number of treatment arms and that placebo response rates may be influenced by the number of active treatment arms in a study.

Community Survey of Bipolar Disorder in Canada: Lifetime Prevalence and Illness Characteristics

Objective: This study reports on the lifetime prevalence and illness characteristics of bipolar disorder (BD) in a large, representative sample of Canadians. Method: Data were obtained from the Canadian Community Health Survey: Mental Health and Well-Being. This representative, cross-sectional survey, conducted by Statistics Canada in 2002, examines the mental health of Canadians aged 15 years and over. The national response rate was 77%. We determined the prevalence rate of BD, correlates of a bipolar diagnosis, and illness characteristics. Results: The weighted lifetime prevalence rate of BD was 2.2% (95% confidence interval [CI], 1.94% to 2.37%). Younger age, low income adequacy, lifetime anxiety disorder, and presence of a substance use disorder in the past 12 months were each significantly associated with the presence of a BD diagnosis (P < 0.001 for each). The largest effect found was for the presence of an anxiety disorder (odds ratio 7.94; 95%CI, 6.35 to 9.92). A lifetime history of anxiety disorder was reported by 51.8% (95%CI, 47.1% to 56.5%) of the respondents with BD, with both panic disorder and agoraphobia each being more frequent among women, compared with men (P = 0.01 and P < 0.001, respectively). The mean age at onset of illness was 22.5 years, SD 12.0. Conclusions: According to the estimated lifetime prevalence of BD found in this study, over 500 000 Canadians likely suffer from this condition. Identifying those at highest risk for BD may assist in developing more effective community-based identification and intervention strategies.

Self-Criticism and Dependency in Depressed Patients Treated with Cognitive Therapy or Pharmacotherapy

The current study aimed to assess the role of self-criticism and dependency in response to cognitive therapy (CT) or pharmacotherapy (PT). It was hypothesized that (a) self-criticism would moderate treatment outcome to CT and PT, and (b) the degree of change in self-criticism and the relationship of this change to treatment response would be greater for patients treated with CT than for patients treated with PT. A sample of outpatients with unipolar major depression received either CT (n = 51) or PT (n = 58). Neither pretreatment self-criticism and dependency scores nor self-criticism and dependency change scores were found to predict response to PT. Treatment response to CT, however, was associated with pretreatment self-criticism scores and pre- and post-self-criticism change scores. Although highly self-critical patients were more likely to have a poor response to CT, the degree to which self-criticism was successfully reduced in treatment was shown to be the best predictor of treatment response to CT.

Bipolar disorder, unipolar depression and the Five-Factor Model of Personality.

We examined differences between personality characteristics of euthymic bipolar disorder patients (BD) (n = 34) and recovered unipolar depressed patients (UD) (n = 74) using the taxonomy of the Five-Factor Model of personality (FFM) as measured by composite scales derived from the NEO Personality Inventory (NEO PI) and the revised NEO PI (NEO PI-R). Euthymic BD patients scored significantly higher on the Openness (O) dimension and the Positive Emotions facet of the E dimension than did recovered UD patients. For O, euthymic BD patients scored higher on the Feelings facet. These results suggest not only that euthymic BD patients are more likely to experience positive affects than recovered UD patients, but also that euthymic BD patients are more receptive to their positive and negative feelings than are recovered UD patients.

International Society for Bipolar Disorders Task Force on Suicide: meta-analyses and meta-regression of correlates of suicide attempts and suicide deaths in bipolar disorder.

Bipolar disorder is associated with a high risk of suicide attempts and suicide death. The main objective of the present study was to identify and quantify the demographic and clinical correlates of attempted and completed suicide in people with bipolar disorder.

Major depression and subclinical (grade 2) hypothyroidism

Subclinical hypothyroidism (SCH) has been reported to occur in patients with a variety of affective syndromes. However, the clinical correlates of SCH in patients with major depression have received limited attention. We therefore examined demographic, clinical and treatment response variables in a cohort of patients with unipolar, nonpsychotic major depression with and without SCH. Of 139 subjects, 19 had SCH defined as an elevated basal TSH with normal circulating levels of T3 and T4. Major depression with SCH differed from that without SCH by the presence of a concurrent panic disorder and a poorer antidepressant response.

Estimated prevalence of the seasonal subtype of major depression in a Canadian community sample.

Objective: To examine estimates of lifetime prevalence of seasonal affective disorder (SAD) in Toronto, Ontario. Method Random telephone numbers were generated for the city of Toronto, and 781 respondents completed a telephone interview. Trained nonphysician interviewers conducted all interviews, which involved structured questions for diagnosing major depression. Patterns of symptom change across seasons were evaluated to establish a diagnosis of SAD according to DSM-III-R criteria. Results Correcting for sex and age, the prevalence of SAD defined by DSM-III-R criteria was 2.9% (95%CI, 1.7% to 4.0%), and the overall lifetime prevalence of major depression in the sample was 26.4% (95%CI, 23.3% to 29.4%). Some subjects were contacted for a follow-up interview conducted in person; the positive predictive value for the diagnosis of major depression for the telephone interview was 100%, and the negative predictive value was 93%. Conclusions The seasonal subtype of depression represents 11% of all subjects with major depression, suggesting that SAD is a significant public health concern. The telephone interview demonstrated adequate reliability, indicating that it is appropriate for epidemiological surveys of this nature.

Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder Section 3. Pharmacological Treatments

Background: The Canadian Network for Mood and Anxiety Treatments (CANMAT) conducted a revision of the 2009 guidelines by updating the evidence and recommendations. The scope of the 2016 guidelines remains the management of major depressive disorder (MDD) in adults, with a target audience of psychiatrists and other mental health professionals. Methods: Using the question-answer format, we conducted a systematic literature search focusing on systematic reviews and meta-analyses. Evidence was graded using CANMAT-defined criteria for level of evidence. Recommendations for lines of treatment were based on the quality of evidence and clinical expert consensus. “Pharmacological Treatments” is the third of six sections of the 2016 guidelines. With little new information on older medications, treatment recommendations focus on second-generation antidepressants. Results: Evidence-informed responses are given for 21 questions under 4 broad categories: 1) principles of pharmacological management, including individualized assessment of patient and medication factors for antidepressant selection, regular and frequent monitoring, and assessing clinical and functional outcomes with measurement-based care; 2) comparative aspects of antidepressant medications based on efficacy, tolerability, and safety, including summaries of newly approved drugs since 2009; 3) practical approaches to pharmacological management, including drug-drug interactions and maintenance recommendations; and 4) managing inadequate response and treatment resistance, with a focus on switching antidepressants, applying adjunctive treatments, and new and emerging agents. Conclusions: Evidence-based pharmacological treatments are available for first-line treatment of MDD and for management of inadequate response. However, given the limitations of the evidence base, pharmacological management of MDD still depends on tailoring treatments to the patient.