Is adjunctive open-label zonisamide effective for bipolar disorder?

OBJECTIVE: To assess the effectiveness and safety of zonisamide in bipolar disorder. METHODS: A chart review was conducted of naturalistic treatment with zonisamide in 35 outpatients meeting DSM-IV criteria for bipolar disorder (9 males, 26 females; mean +/- SD age = 29.2 +/- 12.7; 14 with bipolar disorder type I, 6 with bipolar disorder type II, and 14 with bipolar disorder not otherwise specified). Patients received zonisamide adjunctive therapy between January 1994 and December 2004. Treatment response was defined as a Clinical Global Impressions - Improvement (CGI-I) scale score of +2 (much improved) or + 3 (very much improved). RESULTS: Zonisamide was moderately to markedly effective in 9 subjects (26%). Indication for treatment included depressive (34.3%, [12/35]), manic/hypomanic (28.6%, [10/35]), or mixed (31.4%, [11/35]) symptoms. The mean zonisamide dose was 130 mg/d for a mean duration of treatment of 27.0 +/- 32.3 weeks. Sedation (25%, [4/16]) was the most common side effect; 19/35 (54.3%) reported no side effects. 17/35 (49%) patients terminated early, mostly due to adverse effects (6/35). Using a multivariable model, predictors of response, concurrent mood stabilizers, dose and bipolar subtype (bipolar type I > type II/NOS), were controlled for in this sample. CONCLUSIONS: In 35 persons with bipolar disorder taking standard mood stabilizers and other psychotropic agents, adjunctive zonisamide appears to have modest benefit in global improvement when added to a pre-existing complex medication regimen in patients with bipolar spectrum disorder. These pilot data support the need for larger studies to test the potential efficacy of zonisamide for treatment in mood disorders.

Long-term lamotrigine plus lithium for bipolar disorder: One year outcome.

OBJECTIVE: To obtain pilot data in an observational setting on the use of lamotrigine plus lithium in the long-term treatment of patients with bipolar disorder, 87% of whom had failed to respond to at least one previous mood stabilizer. METHODS: Charts of 21 patients (11 females, 10 males, mean age 43.2 years) treated with the combination of lithium and lamotrigine were reviewed retrospectively for treatment response using the Clinical Global Impression-Bipolar Disorder-Improvement scale, divided into benefit for acute depressive symptoms, acute manic symptoms, and overall illness (including prophylaxis of mood episodes). Of the 21 patients, 76% were diagnosed with bipolar I disorder, and depressive symptoms were the most common acute indication for treatment (52%). Mean doses of lithium and lamotrigine were 963 mg/day and 179 mg/day, respectively, used for a mean of 55.7 weeks. RESULTS: Acute antidepressant benefit was observed in 48% of patients, acute anti-manic benefit in 14%, and overall prophylactic benefit in 29%. Side effects were observed in 38%, with cognitive problems most common (29%). 48% discontinued combination therapy, mainly due to lack of efficacy (19%) or activation of manic-like symptoms (19%). CONCLUSIONS: Among a group of largely treatment-resistant bipolar patients, the combination of lithium and lamotrigine appeared effective for acute depressive symptoms in about half of the patients, but acute anti-manic and long-term prophylactic efficacy appeared less robust.

Sensitivity and specificity of a new bipolar spectrum diagnostic scale.

OBJECTIVE: To assess the sensitivity and specificity of a self-report questionnaire for bipolar disorder, the Bipolar Spectrum Diagnostic Scale (BSDS). METHODS: The BSDS was administered to 68 consecutive patients with bipolar illness and 27 consecutive patients with unipolar major depressive disorder. Created by Ronald Pies, it consists of a descriptive story that captures subtle features of bipolar illness, to which patients may assent on a sentence-by-sentence basis. BSDS scores were compared to clinicians' DSM-IV-based diagnoses. RESULTS: Sensitivity of the BSDS was 0.76, approximately equal in bipolar I and II/NOS subjects (0.75 and 0.79, respectively). The BSDS identified 85% of unipolar-depressed patients as not having bipolar spectrum illness. A shift in the threshold of the BSDS resulted in a large increase in specificity (from 0.85 to 0.93), without a significant loss of sensitivity. CONCLUSIONS: The BSDS was highly sensitive and specific for bipolar spectrum illness, especially with the amended threshold for positive diagnosis.

Sensitivity and specificity of the Mood Disorder Questionnaire for detecting bipolar disorder.

BACKGROUND: This study aims to replicate the sensitivity and specificity of the Mood Disorder Questionnaire (MDQ) for bipolar disorder and assess the impact of insight on the MDQ's sensitivity. Unlike prior telephone-based validation, this is the first clinical study to assess the validity of the MDQ. METHODS: 37 consecutive patients with bipolar spectrum illness received the MDQ, as well as 36 consecutive patients with unipolar depression. MDQ diagnoses were compared to DSM-IV-based SCID diagnoses. A total of 16 bipolar patients also received the Scale to Assess Unawareness of Mental Disorder (SUMD) to measure insight. RESULTS: Overall sensitivity for the MDQ was 0.58, higher in bipolar I disorder (0.69) than in bipolar II/NOS (0.30, P=0.06). The sample was highly insightful, but the two patients with lowest insight both had false negative screens. Patients' low ratings of severity of mania (question 3 of the MDQ) explained almost half of all false negative results. Specificity was 0.67. CONCLUSIONS: The MDQ demonstrates good sensitivity in insightful patients with bipolar I disorder, but may be less useful in patients with impaired insight or milder bipolar spectrum conditions.

Oxcarbazepine treatment of bipolar disorder.

OBJECTIVE: To assess the effectiveness and safety of oxcarbazepine in bipolar disorder. METHOD: A chart review of naturalistic treatment with oxcarbazepine in 42 outpatients with DSM-IV bipolar disorder (10 males, 32 females; mean +/- SD age = 33.3 +/- 12.4 years; 25 with bipolar disorder type I, 4 with bipolar disorder type II, and 13 with bipolar disorder not otherwise specified) was conducted. Patients had received oxcarbazepine monotherapy or adjunctive therapy between April 2000 and April 2002. Treatment response was defined as a Clinical Global Impressions-Improvement scale score of 1 (marked improvement) or 2 (moderate improvement). RESULTS: Oxcarbazepine was moderately to markedly effective in 24 subjects (57%). Mixed symptoms were the most common indication (52% [22/42]). The mean oxcarbazepine dose was 1056.6 mg/day, and mean treatment duration was 16.2 weeks. Sedation (17/42, 40%) was the most common side effect, but 16 patients (38%) had no side effects. Twenty-two patients (52%) stopped treatment, mostly due to side effects (12/22). Males were more likely to respond than females (10/10 vs. 14/32, p =.006). Dose, bipolar subtype, indication, past nonresponse to mood stabilizers, concurrent mood stabilizer use, and monotherapy use of oxcarbazepine did not differentially predict response. CONCLUSION: Oxcarbazepine appeared effective in about one half of patients with bipolar disorder and was well tolerated.