Leverich Gs

Psychosis in bipolar disorder: phenomenology and impact on morbidity and course of illness.

Although psychosis is common in bipolar disorder, few studies have examined the prognostic significance of psychotic features. In addition, some studies suggest that the presence of mood-incongruent psychosis, in particular, is associated with poorer outcome compared with mood-congruent psychosis. We assesses the phenomenology and prevalence of mood-congruent and mood-incongruent psychotic symptoms in 352 patients with bipolar I disorder participating in the Stanley Foundation Bipolar Treatment Network. We compared the demographic and clinical features, and measures of psychosocial and vocational functioning in patients with and without a history of psychosis. The phenomenology of psychosis in this cohort of patients with bipolar disorder was similar to that reported in earlier studies and supported the lack of diagnostic specificity of any one type of psychotic symptom. There were no significant differences between patients with and without a history of psychosis on any demographic, psychosocial, vocational, or course of illness variables. Only family history of bipolar disorder was significantly more common in patients with nonpsychotic bipolar disorder compared to patients with a history of psychosis. Among bipolar patients with a history of psychosis, only the proportion of women and lifetime prevalence rates of anxiety disorders occurred significantly more in patients with mood-incongruent delusions. In this large cohort of outpatients with bipolar I disorder, neither a history of psychosis nor of mood-incongruent psychosis had prognostic significance at entry into the Network. The lack of observable prognostic impact may have been, in part, due to the relatively high morbidity and poor functional outcome of a substantial portion of the total cohort.

Preliminary evidence of the reliability and validity of the prospective life-chart methodology (LCM-p).

This article describes the use of the NIMH prospective life-charting methodology (NIMH LCM-p) in the context of a formal double-blind, clinical trial and provides preliminary evidence of its reliability and validity. Subjects included in this report were 30 outpatients with bipolar I and II disorder who completed the first 2 years of a long-term maintenance study: 1 year on carbamazepine or lithium and a crossover to the other in the second year. The LCM-p follows the same types of guidelines and principles utilized in the previously described retrospective life-chart process, allowing for continuity of illness assessment prior and subsequent to study entry. In the LCM-p, daily ratings of severity of mood symptoms based on the degree of associated functional incapacity, provide a more detailed topography of manic and depressive fluctuations. Inter-rater reliability was examined by comparing the severity of daily LCM-p ratings assigned by two raters. In order to assess the validity, we correlated the LCM-p ratings with well-standardized scales, including Hamilton and Beck Depression Ratings, Young Mania Ratings and the Global Assessment Scale (GAS). The Kappa scores for inter-rater reliability demonstrated significant and satisfactory strength of agreement with no fall off over 14 days prior to the rating interview. Strong correlations were found: (1) between the LCM-p average severity for depression rating and the mean Hamilton Depression Rating (r = 0.86, p < .001), and the Beck Depression Inventory (r = 0.73, p < .001); 2) between the LCM-p average severity for mania rating and the Young Mania Rating Scale (r = 0.61, p < .001); and (3) between the LCM-p average severity and the GAS (r = -0.81, p < .001). These preliminary data suggest the reliability and validity of the NIMH-LCM-p in assessing manic and depressive episode severity. It also provides a useful continuous daily measure of affective illness-related symptom fluctuations that allows for detailed prospective assessment of frequency and pattern of illness, treatment response, and continuity with retrospective life chart assessments.

Olanzapine in treatment-resistant bipolar disorder

BACKGROUND We evaluated the response to olanzapine in 14 consecutive patients with bipolar I disorder who were inadequately responsive to standard psychotropic agents. METHODS Fourteen patients with bipolar I disorder by DSM-IV criteria experiencing persistent affective symptoms inadequately responsive to at least one standard mood stabilizer were treated with open-label olanzapine by one of the authors. Response was assessed with the Clinical Global Impression Scale modified for use in bipolar disorder (CGI-BP). RESULTS The 14 patients received olanzapine at a mean (SD dosage of 14.1+/-7.2 (range 5-30) mg/day for a mean+/-SD of 101.4+/-56.3 (range 30-217) days of treatment. Of the 14 patients, 8 (57%) displayed much or very much overall improvement in their illness. In general, olanzapine was well tolerated. The most common side effects were sedation, tremor, dry mouth, and appetite stimulation with weight gain. LIMITATIONS Data were obtained nonblindly and without a randomized control group, and olanzapine was added to ongoing psychotropic regimens. CONCLUSION Olanzapine may have antimanic and mood-stabilizing effects in some patients with bipolar disorder, and is generally well tolerated. Controlled studies of olanzapine in bipolar disorder appear warranted.

A History of the Use of Anticonvulsants as Mood Stabilizers in the Last Two Decades of the 20th Century

Anticonvulsants have moved into an important position as alternatives and adjuncts to lithium carbonate in the treatment of bipolar illness. Work with the nonhomologous model of kindled seizures helped in the choice of carbamazepine as a potential mood stabilizer and in the study of the mechanisms of action of the second generation anticonvulsants carbamazepine and valproate, as well as the putative third generation psychotropic anticonvulsants lamotrigine and gabapentin. Anticonvulsant neuropeptides such as TRH and nonconvulsant approaches with repeated transcranial magnetic stimulation (rTMS) also appear promising.

Lamotrigine for the treatment of bipolar disorder: A clinical case series

BACKGROUND Recently, a number of new agents have become available to treat bipolar disorder, however many patients may not respond fully even when used in combination. Early reports in epilepsy studies suggested mood-related effects of lamotrigine treatment, as have preliminary reports in bipolar patients. METHODS Seventeen patients meeting DSM-IV criteria for bipolar I (n = 9) or bipolar II (n = 8) disorder displaying affective symptoms and a past history of inadequate response or tolerability to at least two standard mood stabilizing agents were recruited through the Stanley Foundation Bipolar Network and treated with the new anticonvulsant lamotrigine in an add-on, open-label study. Response to therapy was assessed using the Clinical Global Impression Scale modified for bipolar disorder. RESULTS The mean dose of lamotrigine was 187+/-157 mg/day (range 50-600 mg/day) for a mean duration of 159+/-109 days (range 14-455 days). Eleven (65%) patients were rated as very much or much improved. Lamotrigine was well tolerated, and may have mood stabilizing and antidepressant properties in some patients with bipolar disorder. LIMITATIONS The study is hypothesis generating because it was uncontrolled and open. Controlled studies are warranted. CONCLUSIONS This preliminary report supports clinical improvement for both mood cycling and depression in patients with bipolar disorder treated with lamotrigine.

Tranylcypromine vs. lamotrigine in the treatment of refractory bipolar depression: a failed but clinically useful study

Objective:  To compare the efficacy and tolerability of tranylcypromine vs. lamotrigine in bipolar depression not responding to conventional antidepressants.

Prevalence rate of mixed depression and its impact on remission: a controlled evaluation

Introduction: Comorbid psychiatric diagnoses such as panic disorder and drug and alcohol abuse are common in both major depressive disorder (MDD) and bipolar disorder (BD). Although screening instruments such as the Hypomania Checklist (HCL-32) may be useful in distinguishing between bipolar and unipolar patients, very little work has assessed whether comorbidities, for example, substance abuse, may be related to ratings of hypomanic symptoms on such instruments. In this study we assess whether a lifetime diagnosis of comorbid panic disorder, drug abuse, alcohol abuse or alcohol dependence in patients with MDD is associated with increased ratings of hypomanic symptoms on the HCL-32. Methods: 50 patients with MDD (according to DSM-IV) recruited from out-patient psychiatric services were assessed for a range of diagnoses according to the Mini International Neuropsychiatric Interview (MINI). Subjects also completed a detailed structured clinical assessment and the HCL-32 questionnaire. A number of previous reports have found that a score of 14 or more on the HCL-32 is an optimal threshold for the correct identification of bipolar disorder (with a sensitivity of 80% and specificity 51%) so this threshold was applied to our sample of MDD patients. Two groups were identified according to whether they scored above or below 14 on the HCL-32 and were compared on rates on lifetime comorbid diagnosis of panic disorder, drug abuse, alcohol abuse and alcohol dependence. Results: 27 out of 50 MDD patients (54%) scored above the threshold of 14 or more on the HCL-32. There were no significant differences between these subjects and subjects not meeting the threshold on rates of comorbid panic disorder (48.1% versus 47.8%; OR = 1.01, 95%CI 0.60–1.68), drug abuse (7.4% versus 4.3%; OR = 1.25, 95%CI 0.54–2.92) or alcohol abuse (37.0% versus 21.7%; OR = 1.37, 95%CI 0.84–2.25). However, subjects scoring above the threshold had significantly higher rates of comorbid alcohol dependence (18.5% versus 0%; OR = 2.05, 95%CI 1.52–2.76). Discussion: 54% of MDD patients in this sample scored above the threshold of 14 on the HCL-32, suggestive of a bipolar diagnosis. Cormorbid alcohol dependence was significantly associated with scoring above the threshold. In fact, all of the MDD patients in this sample who also had a lifetime history of alcohol dependence scored 14 or more on the HCL-32. Future studies involving screening measures for bipolar disorder, particularly the HCL-32, should carefully consider the role played by comorbidities such as alcohol dependence.