Oxcarbazepine add-on in the treatment of refractory bipolar disorder.

OBJECTIVE: To assess the effectiveness and safety of oxcarbazepine (OXC) in bipolar disorder (BD) and related conditions. METHODS: We reviewed medical records of patients given OXC treatment between March 2003 and March 2005 at the University of British Columbia Hospital. Response to treatment was assessed retrospectively using the Clinical Global Impression of Severity (CGI-S), and the Clinical Global Impression of Improvement (CGI-I) scales. RESULTS: OXC was prescribed to 15 patients with bipolar I (n = 12), bipolar II (n = 2) and schizoaffective (n = 1) disorder who presented with depression (n = 9), mania (n = 3), hypomania (n = 1), or mixed state (n = 2). Six patients had Axis II diagnoses and 10 patients had a family history of mood disorders. Psychiatric co-morbidity was found in four patients. The mean daily dose of OXC was 775 +/- 556.11 mg/day and the mean duration of follow-up was 31.60 +/- 41.51 weeks. The OXC add-on led to a significant reduction in symptoms as indicated by reduction in CGI-S scores at 1 and 2 months. Nine of 12 patients at 1 month and seven of 14 at 1 or 2 months were much or very much improved on CGI-I scale. One patient (7%) developed hyponatremia. Six patients (40%) experienced no side effects and three patients (20%) stopped the medication because of side effects. CONCLUSION: OXC was effective and well-tolerated in refractory BD and schizoaffective disorder. These preliminary data are promising but controlled studies are needed to confirm its efficacy in refractory BD.

A positron emission tomography study of the effects of treatment with valproate on brain 5-HT2A receptors in acute mania.

OBJECTIVE: To examine the effects of treatment with valproate on brain 5-HT2A receptors in acute manic patients using positron emission tomography (PET) and [18F]-setoperone. METHODS: Patients with DSM-IV bipolar I disorder-manic episode were recruited. Patients were drug free or drug naïve at the time of baseline PET scan. All patients were treated with valproate and one patient received lithium in addition to valproate for 3-5 weeks following which they had a post-treatment PET scan. The effect of treatment on brain 5-HT2A receptor binding was determined using statistical parametric mapping (SPM) and region of interest (ROI) analyses. Of the 12 manic patients recruited, seven patients had both baseline and post-treatment PET scans. RESULTS: All seven patients improved with treatment and were in remission at the time of the second PET scan. Both SPM and ROI analyses showed that treatment with mood stabilizers had no significant effect on brain 5-HT2A receptor binding in manic patients. CONCLUSION: This study suggests that changes in brain 5-HT2A receptors are not involved in the antimanic effects of mood stabilizers however, we cannot exclude the possibility of 5-HT2A receptor involvement in down-stream signaling pathways.

Generic and health-related quality of life in patients with seasonal and nonseasonal depression.

Although a relatively large body of research has now accumulated concerning the relationship between quality of life (QoL) and nonseasonal depression, there is a dearth of information about QoL in seasonal affective disorder (SAD). The aim of this study was to compare perceived levels of broad ('generic') and health-related QoL in patients with seasonal and nonseasonal depression. Participants were 72 patients with SAD enrolled in an on-going multicentre study in Canada, and 72 patients with nonseasonal major depressive disorder (MDD) matched for severity of depression attending an outpatient psychiatric clinic in Vancouver, British Columbia. All participants completed two measures of QoL (the 20-item Medical Outcomes Study [MOS] Short-Form General Health Survey [SF-20] and the Quality of Life Enjoyment and Satisfaction Questionnaire [Q-LES-Q]) at baseline prior to treatment. The results of the study indicated that both generic and health-related QoL were compromised in patients with SAD compared with general population norms. For example, mean Q-LES-Q scores (range 0-100, where higher scores indicate better QoL) were 44%, compared with scores of 83% reported for the general population. Patients with nonseasonal depression showed significantly poorer functioning in several domains on the SF-20, but no significant differences in Q-LES-Q scores emerged. Perceived QoL is impaired in patients with SAD. Degree of impairment between seasonal and nonseasonal depressives is equivalent when assessed using the Q-LES-Q, but significant inter-group differences are apparent in SF-20 domain scores. Future research is required to determine whether perceived QoL is improved by treatment interventions for seasonal depression such as light therapy or antidepressant medication.

Citalopram and bupropion-SR: combining versus switching in patients with treatment-resistant depression.

OBJECTIVE: There are limited data comparing medication strategies in patients with treatment-resistant depression. In this study, we compared the effects of combining citalopram and bupropion-SR versus switching to the other monotherapy in treatment-resistant depression. METHOD: This was a naturalistic, open-label cohort study. Patients with DSM-IV major depressive disorder who had not responded to at least 1 previous antidepressant and at least 6 weeks of treatment with citalopram or bupropion-SR were treated in a standard clinical protocol. In alternate months, eligible consecutive patients were treated by adding citalopram or bupropion-SR, or by switching to the other medication. Patients were assessed at baseline and after 6 weeks of treatment with the 29-item version of the Structured Interview Guide for the Hamilton Depression Rating Scale, Seasonal Affective Disorders Version (SIGH-SAD). RESULTS: A total of 61 patients completed the study: 32 in the combination condition and 29 in the monotherapy switch condition. The combination condition was superior to the monotherapy switch in the SIGH-SAD change score (-14.8 vs. -10.1, respectively, p <.04) and the proportion of patients in clinical remission (28% vs. 7%, p <.05). There were no differences in the proportion of patients who had side effects or in the severity of the side effects experienced. CONCLUSION: The results of this cohort study suggest that combining citalopram and bupropion-SR is more effective than switching to a monotherapy. Combination treatment was well tolerated with no greater side effect burden than monotherapy. Limitations of this study include the nonrandomized design, open-label treatment, and small sample size.

The influence of selective serotonin reuptake inhibitors on human platelet serotonin.

Clinical depression has been proposed to be an independent risk factor for cardiovascular disease. While it is suggested that selective serotonin reuptake inhibitors (SSRIs) reduce the risk of acute cardiovascular problems of depressed patients, the effect of SSRIs on platelets, the only blood cells committed to serotonin (5-HT) transport, remains largely unknown. The goal of this pilot study was to measure the 5-HT levels in platelets of untreated and SSRI-treated depressed patients and normal subjects and to determine whether the interaction of SSRIs with platelets can explain their possible cardiovascular benefit in patients with depression. Platelet 5-HT was determined by an immunocytochemical assay and high-pressure liquid chromatography with electrochemical detection (HPLC-ECD). In normal control subjects without cardiovascular disease, 78 +/- 8% of platelets were 5-HT-positive (n = 14). Depression caused a significant reduction in platelet 5-HT to 46 +/- 21% in untreated patients (n = 13) and 22 +/- 13% in SSRI-treated patients (n = 14). As a class, all selective serotonin reuptake inhibitors significantly reduced the 5-HT concentration in patient platelets. An inverse relationship of 5-HT level and dose of medication might be suggested. These results correlated well with 5-HT data from HPLC (r = 0.8509, p < 0.001). SSRIs did not affect platelet aggregation and dense granule release in response to thrombin, but significantly reduced ADP-induced platelet aggregation and dense granule release in both patient and normal control samples. The active inhibition of platelet aggregation by SSRIs might explain their cardiovascular benefit.

Mirtazapine for treatment-resistant depression: a preliminary report.

OBJECTIVE: To describe the effectiveness and tolerability of mirtazapine, a noradrenergic and specific serotonergic antidepressant, in the open-label treatment of patients with depression who were resistant to other antidepressant agents. METHODS: The charts of 24 patients who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, (DSM-IV) criteria for major depressive disorder and were treated with mirtazapine after partial or nonresponse to standard antidepressants were reviewed for clinical response. Outcome was determined by using the Clinical Global Impressions of Improvement (CGI-I) Scale. RESULTS: Symptomatic improvement was observed in 9 (38%) of 24 patients during an average of 14.1 months of mirtazapine treatment at a mean dose of 36.7 mg/day. Five (21%) patients discontinued mirtazapine because of side effects such as fatigue, weight gain and nausea. Five (21%) patients were receiving combination therapy with another antidepressant when mirtazapine treatment was initiated. CONCLUSIONS: This open-label study suggests that a subgroup of patients with treatment-resistant depression may benefit from mirtazapine treatment. Further controlled studies are required to demonstrate the efficacy of mirtazapine in treatment-resistant depression.

Measuring change in psychiatric symptoms using the Neuropsychiatric Inventory: Nursing Home version.

BACKGROUND: The Neuropsychiatric Inventory-Nursing Home version (NPI-NH) is a modified version of the Neuropsychiatric Inventory (NPI). Accurate interpretation of change in the symptom ratings on the NPI-NH, as with any measure, is a concern for both clinicians and researchers. The purpose of this article is to present data for the interpretation of reliable change in the NPI-NH scores for acute geriatric neuropsychiatry patients. METHOD: Fifty-two geriatric psychiatry inpatients were administered the NPI-NH twice, at a 72-hour interval. Standard errors of difference scores were used to calculate confidence intervals for each of the NPI-NH subscales and the total score. RESULTS: Based on the calculations described above, estimates of reliable change on the individual subscales ranged from plus or minus 1.29 points on the Euphoria/Elation subscale to 5.13 points on the Anxiety subscale. Statistically meaningful change on the Agitation and the Apathy subscales was established at 4.0 and 4.3 points, respectively. A change in the total score of plus or minus 22 points is required to exceed the possible range of measurement error, at a 0.80 confidence interval (CI). CONCLUSIONS: Overall, the results of this study indicate that the clinician evaluating elderly psychiatric inpatients should interpret a change in the total score of less than 22 points with caution, because it may be due to measurement error.

ECT: use in individuals with mental retardation.

Electroconvulsive therapy (ECT) is an effective treatment of a variety of serious psychiatric and neurologic disorders. There are infrequent case reports of its use in individuals with mental retardation (MR). We describe 10 patients with MR and complex comorbid psychiatric disorder treated with ECT. Seven patients had an excellent response to treatment. Side effects of treatment were minimal and transitory.