Lamotrigine adjunctive treatment in resistant unipolar depression: an open, descriptive study

Adjunctive treatment of lamotrigine compared to other antidepressants in the treatment of partially responsive, poorly functioning patients with unipolar depression was assessed. Fourteen consenting patients with confirmed DSM-IV-R diagnosis of unipolar depression were identified as treatment resistant. All patients failed at least two 8-week treatment trials with antidepressants. All were treated with lamotrigine as an adjunct to other antidepressants for at least 6 months. The primary effectiveness measure was the Clinical Global Impression Severity subscale (CGI-S). Other scales included the Montgomery-Asberg Depression Scale (MADRS) and the Global Assessment of Functioning Scale (GAF). Monitoring for skin rashes, headache, dizziness, somnolence, and gastrointestinal disturbances was carried out to assess for adverse events. Baseline measures prior to adding lamotrigine were compared to those at 8 weeks and 6 months with adjunctive treatment. Twelve patients of the total (n=14) completed the trial, and two discontinued treatment. There was significant, rapid, and robust resolution in symptoms in all effectiveness measures, including the core symptoms of depression, as shown by the changes from baseline in CGI-S, and MADRS at 8 weeks. Social and occupational functioning was significantly improved at 6 months. Eight patients returned to gainful employment or started schooling. Patients tolerated the adjunctive lamotrigine treatment well. Lamotrigine may have antidepressant properties in patients with unipolar depression and may have an earlier onset of action when given in combination with antidepressants.     

A 52-week, open-label continuation study of lamotrigine in the treatment of bipolar depression

BACKGROUND: Lamotrigine has demonstrated efficacy for the acute treatment of depression in bipolar I patients in a placebo-controlled, monotherapy study. We describe the results of a 52-week, open-label continuation of that trial. METHOD: Patients meeting DSM-IV criteria for bipolar I disorder with a current major depressive episode who completed a 7-week, double-blind study of bipolar depression were offered 1 year of open-label lamotrigine therapy (flexible doses of 100-500 mg/day) in a continuation study. To maintain the acute study blind, the first 3 weeks of the continuation study remained blinded while patients previously randomly assigned to placebo were titrated to a lamotrigine dose of 50 mg/day. Patients who had been randomly assigned to lamotrigine continued at their fixed doses. Beginning at week 4, all patients received open-label lamotrigine for up to 49 additional weeks. Concomitant psychotropic medications were permitted during the open-label phase. Effectiveness (Montgomery-Asberg Depression Rating Scale [MADRS], Clinical Global Impressions-Improvement scale) and safety assessments were administered at weeks 4, 12, 24, 36, and 52. The study was conducted from June 1996 to December 1998. RESULTS: Of 135 patients completing the acute study, 124 (92%) entered the continuation study: 77 had received lamotrigine and 47 had received placebo in the acute study. The mean duration of lamotrigine exposure was 10.4 months, with a mean modal dose of 187 mg/day. Sixty-nine patients (56%) completed 1 year of treatment. Significant and sustained improvement from baseline was seen in mean observed MADRS scores (p <.05). The proportion of patients achieving remission (MADRS score < or = 11) by week 4 of the study was 81.4%, and episodes of mania/hypomania occurred less frequently than in the preceding year. Headache was the most common drug-related adverse event. CONCLUSION: During 1 year of open-label therapy with lamotrigine as adjunctive therapy or monotherapy, bipolar I patients experienced sustained improvement in depressive symptoms without evidence of mood destabilization.     

Immunotherapy with interferon-alpha in patients affected by chronic hepatitis C induces an intercorrelated stimulation of the cytokine network and an increase in depressive and anxiety symptoms.

Immunotherapy with interferon-alpha (IFNalpha) may induce depressive symptoms, anxiety and major depression when administered for at least 1-3 months at a dose of 3-10 MUI daily, twice or three times a week. Previously, it has been shown that immunotherapy with interleukin-2 (IL-2) significantly induces the cytokine network, as measured by increases in serum IL-6, IL-10 and the IL-2 receptor (IL-2R), and that the immunotherapy-induced changes in the cytokine network are significantly correlated with the increases in depression ratings. The main aim of this study was to examine the effects of immunotherapy with IFNalpha on the cytokine network in relation to changes in depression and anxiety ratings. Fourteen patients, affected by chronic active C-hepatitis, were treated with IFNalpha (3-6 MUI s.c. three/six times a week for 6 months) and had measurements of serum IFN-gamma (IFNgamma), IL-2, IL-6, IL-6R, IL-8 and IL-10 before starting therapy and 2, 4, 16 and 24 weeks after immunotherapy with IFNalpha. Severity of depression and anxiety were measured with the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Rating Scale (HAM-A), respectively. Repeated measure (RM) design ANOVAs showed significantly higher MADRS and HAM-A scores 2-4 weeks and 4-6 months after starting IFNalpha-based immunotherapy than at baseline. RM design ANOVAs showed significantly higher serum IL-6 and IL-8 levels 2-4 weeks after starting IFNalpha-based immunotherapy and higher serum IL-10 levels 2-4 weeks and 4-6 months after starting therapy than at baseline. There were significant relationships between the IFNalpha-induced changes in serum IL-6 or IL-8 and the depression and anxiety scores. The findings show that IFNalpha-based immunotherapy induces the cytokine network and that IFNalpha-induced increases in IL-6 predicts the development of depressive symptoms. Depressive symptoms following IFNalpha treatment may be secondary to cytokine induction, including that of IL-6.     

Zuclopenthixol decanoate and haloperidol decanoate in chronic schizophrenia: a double-blind multicentre study.

Zuclopenthixol decanoate (ZPT-D) and haloperidol decanoate (HAL-D) were compared in the maintenance treatment of chronic schizophrenic patients. All patients were treated with either ZPT-D or HAL-D for at least 3 months and were then randomly allocated to treatment with either ZPT-D (100-600 mg every 4 weeks) or HAL-D (38-200 mg every 4 weeks) for 9 months. Sixty-four patients entered the study. Three patients were only assessed at baseline. Four patients in the HAL-D group were withdrawn because of deterioration. One patient in the ZPT-D group committed suicide. Fifty-six patients completed the trial. The assessment programme comprised Clinical Global Impressions by psychiatrists and nurses, the Brief Psychiatric Rating Scale (BPRS), Montgomery-Asberg Depression Rating Scale (MADRS), UKU Side Effect Scale and Simpson-Angus Scale, Ratings were made at baseline and after 12, 24 and 36 weeks of treatment. The severity of illness scores remained almost constant. The only between-group difference was recorded at month 6 in favour of ZPT-D. The BPRS total scores were reduced significantly in both groups with no between-group differences. The depression scores on the MADRS were very low. Both treatments caused few and mild side effects according to the UKU Side Effect Scale and the Simpson-Angus scale, and there were no significant differences between the groups. Both ZPT-D and HAL-D seem to be effective in the maintenance treatment of chronic schizophrenic patients and cause few side effects. The injections of ZPT-D and HAL-D can be given at 4-week intervals.     

Greater depression severity associated with less improvement in depression-associated cognitive deficits in older subjects.

OBJECTIVES: Elderly depressed patients often exhibit cognitive deficits, which may improve with drug therapy. The authors investigated the relationship of baseline depression severity and cognitive improvement with antidepressant treatment in depressed patients with mild cognitive impairment. METHODS: Mini-Mental State Exam (MMSE) and Montgomery-Asberg Depression Rating Scale (MADRS) scores were measured in 52 depressed geriatric patients without dementia at baseline, 6, and 12 months, during an intent-to-treat period. A repeated-measures regression model tested the effect of MADRS score on MMSE. RESULTS: MMSE changes were significant and linear over time, with an average increase of 0.72 in the MMSE per 6-month interval. The final model showed that for every point increase in baseline MADRS, the average 6-month increase in MMSE decreased by 0.12. Repeated MADRS measurements did not significantly alter its predictive value. CONCLUSION: Greater baseline depression severity in older subjects with mild cognitive deficits is associated with less improvement in those deficits even with successful antidepressant therapy.     

Lamotrigine in the acute treatment of bipolar depression: results of five double-blind, placebo-controlled clinical trials

OBJECTIVES: The efficacy of lamotrigine as maintenance treatment for bipolar disorder (BD), particularly for delaying depressive episodes, is well established, but its efficacy in the acute treatment of bipolar depression is less clear. This paper reports the results of five randomized, double-blind, placebo-controlled trials of lamotrigine monotherapy for the acute treatment of bipolar depression. METHODS: Adult subjects with bipolar I or II disorder experiencing a depressive episode were randomized to placebo or lamotrigine monotherapy (after titration, at a fixed dose of 50 mg or 200 mg daily in Study 1; a flexible dose of 100-400 mg daily in Study 2; or a fixed dose of 200 mg daily in Studies 3, 4 and 5) for 7-10 weeks. RESULTS: Lamotrigine did not differ significantly from placebo on primary efficacy endpoints [17-item Hamilton Depression Rating Scale in Studies 1 and 2; Montgomery-Asberg Depression Rating Scale (MADRS) in Studies 3, 4 and 5]. In Study 1, lamotrigine significantly separated from placebo on some secondary measures of efficacy, including the MADRS, the Clinical Global Impressions-Severity (CGI-S) and the CGI-Improvement (CGI-I), but seldom differed on secondary efficacy endpoints for the other studies. CONCLUSIONS: Lamotrigine monotherapy did not demonstrate efficacy in the acute treatment of bipolar depression in four out of five placebo-controlled clinical studies. Lamotrigine was well tolerated in the acute treatment of bipolar depression.     

Effect of augmentation with olanzapine in outpatients with depression in partial remission with melancholic features: consecutive case series

The aim of the present 12-week, open-label study was to investigate the effect of olanzapine augmentation in outpatients with depression with melancholic features who demonstrated partial response to standard antidepressants but who were reluctant to change antidepressants. The subjects consisted of 22 outpatients meeting the DSM-IV-TR criteria for major depression. Olanzapine was initially added at 2.5 mg/day and the dose was adjusted according to the clinical condition. Data were analyzed using an intention-to-treat methodology. A paired t-test was used to compare total Montgomery Asberg Depression Rating Scale (MADRS) scores before treatment, at baseline (prior to olanzapine), and 4, 8, and 12 weeks after starting olanzapine. Of 22 enrolled patients, 20 completed the trial. The mean (±SD) MADRS score was 17.1 ± 1.0 at baseline and decreased significantly to 8.1 ± 3.2 at 4 weeks after the administration of olanzapine. This significant reduction continued until 12 weeks, when the mean MADRS score was 4.9 ± 2.9, indicating full remission. These results suggest that olanzapine augmentation may be useful for patients with depression in partial remission. A controlled, double-blind trial, however, is needed to confirm these preliminary findings.     

Lower activities of serum peptidases predict higher depressive and anxiety levels following interferon-alpha-based immunotherapy in patients with hepatitis C

OBJECTIVE: There is evidence that in patients with chronic hepatitis C, immunotherapy with interferon-alpha (IFN alpha) may induce depression. A lowered activity of peptidases, such as prolylendopeptidase (PEP) and dipeptidyl peptidase IV (DPP IV), occurs in depression. This study examines whether lowered serum PEP or DPP IV activity before starting IFN alpha-based immunotherapy predicts the increase in depressive symptoms during immunotherapy. METHOD: Serum PEP and DPP IV activities are measured in patients with hepatitis C before and 2, 4 and 16 weeks after starting IFN alpha-based immunotherapy. The Montgomery Asberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Rating Scale (HAM-A) are completed. RESULTS: Patients with lower baseline PEP or DPP IV had significantly higher MADRS and HAM-A scores both at baseline and during immunotherapy. Patients with lower baseline DPP IV had significantly higher increases in the MADRS following IFN alpha treatment. CONCLUSION: Lower baseline PEP and DPP IV predict higher depressive and anxiety ratings during IFN alpha-based immunotherapy.     

Effect of levetiracetam on depression and anxiety in adult epileptic patients

BACKGROUND: Interictal depression is common in patients with epilepsy and it significantly impacts quality of life. Some studies indicate that levetiracetam (LEV) may have mood stabilizing properties. METHODS: Twenty-five adults with uncontrolled partial seizures and concomitant depressive symptoms were treated with LEV. Patients were evaluated for depression and anxiety with several psychometric measures, including: Montgomery and Asberg Depression Rating Scale (MADRS), Hamilton Depression Rating Scale (HDRS), Zung Self-rating Scale for Depression (Z-SDS), Hamilton Anxiety Rating Scale (HARS), Zung Self-rating Scale for Anxiety (Z-SAS). RESULTS: Evaluations after 5 weeks and after 3 months of LEV treatment demonstrated significant improvement in depression and anxiety. CONCLUSIONS: This uncontrolled study suggests that treatment with LEV may also improve depression and anxiety in patients with partial seizures. However, the sample of patients is limited and the possibility of a placebo effect cannot be excluded. These findings must be considered preliminary and should be replicated under placebo-controlled conditions.     

A double-blind placebo-controlled study of lamotrigine monotherapy in outpatients with bipolar I depression. Lamictal 602 Study Group

BACKGROUND: More treatment options for bipolar depression are needed. Currently available antidepressants may increase the risk of mania and rapid cycling, and mood stabilizers appear to be less effective in treating depression than mania. Preliminary data suggest that lamotrigine, an established antiepileptic drug, may be effective for both the depression and mania associated with bipolar disorder. This is the first controlled multicenter study evaluating lamotrigine monotherapy in the treatment of bipolar I depression. METHODS: Outpatients with bipolar I disorder experiencing a major depressive episode (DSM-IV, N = 195) received lamotrigine (50 or 200 mg/day) or placebo as monotherapy for 7 weeks. Psychiatric evaluations, including the Hamilton Rating Scale for Depression (HAM-D), the Montgomery-Asberg Depression Rating Scale (MADRS), Mania Rating Scale, and the Clinical Global Impressions scale for Severity (CGI-S) and Improvement (CGI-I) were completed at each weekly visit. RESULTS: Lamotrigine 200 mg/day demonstrated significant antidepressant efficacy on the 17-item HAM-D, HAM-D Item 1, MADRS, CGI-S, and CGI-I compared with placebo. Improvements were seen as early as week 3. Lamotrigine 50 mg/day also demonstrated efficacy compared with placebo on several measures. The proportions of patients exhibiting a response on CGI-I were 51%, 41%, and 26% for lamotrigine 200 mg/day, lamotrigine 50 mg/day, and placebo groups, respectively. Adverse events and other safety results were similar across treatment groups, except for a higher rate of headache in the lamotrigine groups. CONCLUSION: Lamotrigine monotherapy is an effective and well-tolerated treatment for bipolar depression.     

A prospective study of escitalopram in the treatment of major depressive episodes in the presence or absence of anxiety

This open, multicenter, prospective study in France assessed the efficacy and tolerability of escitalopram in patients with depression, with or without comorbid anxiety. Escitalopram was administered over a 12-week treatment period to 790 depressed patients, including 482 patients with at least one concomitant anxiety disorder. The study was completed by 649 patients. At baseline, the mean Montgomery-Asberg Depression Rating Scale (MADRS) total score was 31.5 and decreased to 12.4 at end point (last observation carried forward [LOCF]). The MADRS score decreased by 20.5 points in patients with no anxiety disorder and by 18.3 points in patients with at least one concomitant anxiety disorder. The mean Hamilton Anxiety Rating Scale (HAM-A) total score at baseline was 25.6, which decreased to 10.8 at end point (LOCF). The HAM-A score decreased by 13.8 points in patients with no anxiety disorder and by 15.5 points in patients with at least one anxiety disorder. Adverse events were reported by 246 patients (31%). The most frequent adverse events were nausea in 65 patients (8%) and headache in 38 patients (5%); 61 patients (8%) discontinued treatment due to adverse events. Escitalopram was well tolerated and efficacious in reducing symptoms of depression in patients with or without comorbid anxiety over a 12-week treatment period.     

A multicentre double-blind comparative trial of fluvoxamine versus lorazepam in mixed anxiety and depression treated in general practice

Fluvoxamine, a selective serotonin reuptake inhibitor, was compared with lorazepam in a multicentre double-blind, parallel group study in 112 general practice patients with mixed anxiety and depression. For inclusion, patients were required to have minimum baseline scores of 21 on the Montgomery-Asberg Depression Rating Scale (MADRS) and 11 on the Clinical Anxiety Scale (CAS). Treatment was for 6 weeks. There were no significant differences between treatments at any point except in an elderly subgroup in whom anxiety improved more rapidly with lorazepam. There were significant improvements in MADRS, CAS and global ratings compared with baseline at all subsequent assessments. Improvement continued during the whole treatment period. Lorazepam produced more sedation, whilst fluvoxamine produced significantly more nausea and vomiting; this was usually early in onset and, if tolerated, resolved during the course of the study. As it is now widely recognized that benzodiazepines should only be given in short courses of 2-4 weeks, the continued improvement up to 6 weeks has implications regarding choice of treatment.     

The Liverpool Adverse Events Profile: relation to AED use and mood

PURPOSE: The Liverpool Adverse Events Profile (LAEP) is used as a systematic measure of adverse effects from antiepileptic drugs (AEDs). This study evaluated LAEP in newly diagnosed seizure patients, and examined the relation between LAEP, anxiety, and depression. METHODS: Seizure patients seen in the two First Seizure Clinics were categorized into group A (AEDs commenced after assessment), group B (AEDs commenced before assessment), and group C (no AEDs). LAEP and the Hospital Anxiety and Depression Scale (HADS) were completed at baseline (n=164) and 3 months (n=103). Each LAEP symptom was assessed for baseline frequency, 3-month frequency, and frequency change over a 3-month period. Global scores for LAEP and HADS were analysed at baseline and 3 months. RESULTS: Symptom-reporting patterns were similar between groups. However, increased frequency over a 3-month period occurred for 12 symptoms in group A, 10 in group B, and one in group C. Global LAEP and HADS showed no significant group differences at baseline or changes over a 3-month period. Multiple regression revealed that HADS scores predicted LAEP global scores better than did AED status. Multivariate analyses of variance demonstrated that increased reporting of 16 of 19 LAEP symptoms was significantly related to higher anxiety and depression rates. CONCLUSIONS: In a First Seizure Clinic, LAEP detects changes in specific symptom frequencies when used as a repeated, symptom-by-symptom measure. Increased symptom frequency is associated with diagnostic category/AED treatment, anxiety, and depression. Global LAEP scores do not illustrate differences in symptom reporting between patients.     

Screening for anxiety and depression after stroke: Comparison of the Hospital Anxiety and Depression Scale and the Montgomery and Åsberg Depression Rating Scale

Objective

Anxiety and depression after stroke are frequent, but are often overlooked and not assessed. The aims of the study were to (1) assess the prevalence of anxiety and depression and (2) compare the performance of the Hospital Anxiety and Depression Scale (HADS) and Montgomery and Åsberg Depression Rating Scale (MADRS) as screening instruments for anxiety and depression disorders 4 months after stroke.

Methods

Stroke patients, consecutively admitted to a stroke unit, were assessed with HADS and MADRS 4 months after stroke (n=104). Depression and anxiety disorders were diagnosed using the Structured Clinical Interview for DSM-IV (SCID). Measures were compared in terms of correlations, sensitivity, specificity, positive and negative predictive value, overall agreement, kappa, and ROC curves, using DSM-IV diagnoses of “at least one current significant anxiety disorder” (Anxiety) and “any current depression” (Depression), as the clinical criteria.

Results

Anxiety occurred in 23% of patients and Depression in 19% (13% major depression, 3% minor depression, 4% dysthymia). For Anxiety, the optimal screening cut-off was 4 for HADS-A and 6 for HADS-total; for Depression, optimal cut-offs were 4 for HADS-D, 11 for HADS-total, and 8 for MADRS. At cut-offs commonly used in clinical practice for depression screening (HADS-D: 8, MADRS: 12), the MADRS performed marginally better than the HADS.

Conclusion

Anxiety is as prevalent as depression 4 months after stroke. MADRS and HADS-D perform acceptably as screening instruments for depression, and HADS-A for anxiety after stroke. However, lower HADS cut-offs than recommended for the general population should be considered for stroke patients.     

心理社会干预对康复期精神分裂症病情影响的对照研究

目的探讨心理社会干预配合药物治疗对康复期精神分裂症患者精神症状的影响。方法对120名康复期精神分裂症患者进行病例配对对照的前瞻性研究。试验组60人,服用抗精神病药配合心理社会干预。对照组仅单纯服用抗精神病药物治疗。两组分别在入组时、治疗3个月、6个月、9个月以及12个月时进行大体评定量表、Montgomery-Asberg抑郁量表、阳性症状和阴性症状评定量表、自知力与治疗态度问卷进行评定。结果治疗3个月时,试验组在阳性症状和阴性症状评定量表中的一般精神病理分量表（P=0.039）及思维障碍因子（P=0.043）得分低于对照组,差异有统计学意义。6个月时,试验组在一般精神病理分量表（P=0.03）及反应缺乏因子（P=0.018）的得分低于对照组,差异有统计学意义。9个月时,试验组除了阳性量表和思维障碍因子外,其余各项得分均低于对照组,差异有统计学意义。12个月时,试验组各项得分均低于对照组,差异有统计学意义。结论心理社会干预能更好地改善康复期精神分裂症患者各方面的精神病症状、改善抑郁情绪、提高自知力同时改善大体功能水平。     

A 7-week, randomized, double-blind trial of olanzapine/fluoxetine combination versus lamotrigine in the treatment of bipolar I depression

OBJECTIVE: Determine the efficacy and tolerability of olanzapine/fluoxetine combination (OFC) for treatment of acute bipolar I depression compared with lamotrigine. METHOD: The 7-week, acute phase of a randomized, double-blind study compared OFC (6/25, 6/50, 12/25, or 12/50 mg/day; N = 205) with lamotrigine ([LMG] titrated to 200 mg/day; N = 205) in patients with DSM-IV-diagnosed bipolar I disorder, depressed. The study was conducted from November 2003 to August 2004. RESULTS: Completion rates were similar between treatments (OFC, 66.8% vs. LMG, 65.4%; p = .835). OFC-treated patients had significantly greater improvement than lamotrigine-treated patients in change from baseline across the 7-week treatment period on the Clinical Global Impressions-Severity of Illness scale (primary outcome) (p = .002, effect size = 0.26), Montgomery-Asberg Depression Rating Scale (MADRS) (p = .002, effect size = 0.24), and Young Mania Rating Scale total scores (p = .001, effect size = 0.24). Response rates did not significantly differ between groups when defined as > or = 50% reduction in MADRS score (OFC, 68.8% vs. LMG, 59.7%; p = .073). Time to response was significantly shorter for OFC-treated patients (median days [95% CI] = OFC, 17 [14 to 22] vs. LMG, 23 [21 to 34]; p = .010). There was a significant difference in incidence of "suicidal and self-injurious behavior" adverse events (OFC, 0.5% vs. LMG, 3.4%; p = .037). Somnolence, increased appetite, dry mouth, sedation, weight gain, and tremor occurred more frequently (p < .05) in OFC-treated patients than lamotrigine-treated patients. Weight, total cholesterol, and triglyceride levels were significantly elevated in OFC-treated patients compared with lamotrigine-treated patients (all p < or = .001). CONCLUSIONS: Patients with acute bipolar I depression had statistically significantly greater improvement in depressive and manic symptoms, more treatment-emergent adverse events, greater weight gain, and some elevated metabolic factors with OFC than lamotrigine. Treatment differences were of modest size.     

An open-label, flexible-dose study of memantine in major depressive disorder

OBJECTIVE: To assess the efficacy and safety of flexible-dose memantine in patients with major depressive disorder (MDD). METHODS: In this 12-week, single-center, open-label study, 8 patients with MDD were titrated for 4 weeks to 20 mg/d memantine. Nonresponsive patients were titrated to 30 mg/d (at week 8) or 40 mg/d (at week 10), provided that no dose-limiting adverse events were observed. Outcome measures were the Montgomery-Asberg Depression Rating Scale (MADRS), the Hamilton Depression Rating Scale, the Clinical Global Impression-Severity of Illness and the Clinical Global Impression-Improvement Scales, the Patient Global Evaluation, and the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Major Depressive Episode Checklist. Tolerability and safety assessments were performed throughout the trial. RESULTS: The safety population comprised 8 outpatients with a mean (SD) baseline MADRS score of 31.9 (4.45), indicative of severe depression. Seven subjects completed the study. All patients attained the target dose of 20 mg/d; 3 patients were titrated to 30 mg/d after week 8, and 2 patients were titrated to 40 mg/d after week 10. The mean dosage across all weeks was 18.1 mg. Patients improved on all efficacy measures within 1 week of treatment initiation. The mean improvement peaked at week 8 and was maintained through week 12 (MADRS, 18.5 [10.3]; last-observation-carried-forward). All memantine doses were well tolerated. CONCLUSIONS: Memantine demonstrated early-onset efficacy in patients with MDD. The treatment was well tolerated. This study suggests that double-blind, placebo-controlled studies of memantine in depression are merited.     

Efficacy and tolerability of the novel triple reuptake inhibitor amitifadine in the treatment of patients with major depressive disorder: a randomized, double-blind, placebo-controlled trial

Amitifadine (EB-1010, formerly DOV 21,947) is a serotonin-preferring triple reuptake inhibitor with a relative potency to inhibit serotonin, norepinephrine, and dopamine uptake of ～1:2:8, respectively. This 6-week, multicenter, randomized, double-blind, parallel, placebo-controlled study evaluated the efficacy and tolerability of amitifadine in 63 patients with major depressive disorder. Eligible patients (17-item Hamilton Depression Rating Scale [HAMD-17] ≥ 22 at baseline) were randomized to amitifadine 25 mg twice daily (BID) for 2 weeks, then 50 mg BID for 4 weeks or placebo. Mean baseline scores in the modified intent-to-treat population (n = 56) were 31.4 for the Montgomery-Åsberg Depression Rating Scale (MADRS), 29.6 for the HAMD-17, and 25.4 for the Derogatis Interview for Sexual Functioning – Self Report (DISF-SR). At the end of the 6-week double-blind treatment, estimated least squares mean change from baseline (mixed-model repeated measures [MMRM]) in MADRS total score was statistically significantly superior for amitifadine compared to placebo (18.2 vs. 22.0; p = 0.028), with an overall statistical effect size of ?0.601 (Cohen’s d). Amitifadine also was statistically significantly superior to placebo (p = 0.03) for the Clinical Global Impression of Change – Improvement. An anhedonia factor score grouping of MADRS Items 1 (apparent sadness), 2 (reported sadness), 6 (concentration difficulties), 7 (lassitude), and 8 (inability to feel) demonstrated a statistically significant difference in favor of amitifadine compared to placebo (p = 0.049). No differences were observed between treatments in DISF-SR scores. Amitifadine was well-tolerated. Two patients on each treatment discontinued the study early due to adverse events; however, no serious adverse events were reported. This initial clinical trial in patients with severe major depression demonstrated significant antidepressant activity with amitifadine, including attenuating symptoms of anhedonia, and a tolerability profile that was comparable to placebo. The efficacy and tolerability of amitifadine for major depressive disorder are being investigated in additional clinical trials.     

Effectiveness of mirtazapine for nausea and insomnia in cancer patients with depression

Aims:  The purpose of the present paper was to evaluate the effectiveness of mirtazapine orally disintegrating tablets for nausea and sleep disturbance, which are common and distressing symptoms of cancer.
Methods:  This was a 4-week, prospective, open-labeled study of cancer patients. Assessments were performed at baseline and on days 1, 3, 5, 7, 14, and 28. Primary outcome measures were the Clinical Global Impression scale for nausea/vomiting and the Chonnam National University Hospital–Leeds Sleep Evaluation Questionnaire (C-LSEQ) including total amount of night sleep time. The secondary outcome measures consisted of pain items in the 36-item Short Form Health Survey, the Montgomery–Asberg Depression Rating Scale (MADRS), and the EuroQoL (EQ)-5D. Forty-two cancer patients were enrolled.
Results:  Those with nausea ( n  = 28) improved significantly from day 1. The total night sleep time and each item on the C-LSEQ improved from days 1–5. The scores on the MADRS and the depression/anxiety dimension and visual analog scale of EQ-5D improved significantly from the first week. Pain measures also improved from day 1. Exacerbation of sleepiness developed in approximately one-third of subjects during the initial few days, but disappeared gradually.
Conclusion:  In the present study mirtazapine rapidly improved nausea, sleep disturbance, pain and quality of life, as well as depression in cancer patients. Mirtazapine may be an effective treatment option in managing cancer patients with multiple distressing symptoms, including nausea and sleep disturbance.     

Long-term sertraline treatment and peripheral biochemical markers in female depressed patients

Serotonergic system is implicated in the pathogenesis of depression. Peripheral biochemical markers, platelet serotonin (5-HT) and platelet monoamine oxidase (MAO) activity were determined spectrofluorimetrically at baseline and after 4 and 24 weeks of sertraline (a selective serotonin reuptake inhibitor (SSRI)) treatment in 15 female nonsuicidal, nonpsychotic patients with major depression and compared with 15 drug-free healthy women. The aim of the study was to determine the effects of 4 and 24 weeks of sertraline treatment on platelet 5-HT concentration and platelet MAO activity in depressed patients subdivided according to the treatment response into remitters, responders and nonresponders after 4 and 24 weeks of sertraline treatment based on the 70%, 50-69% and <49% reductions in baseline Montgomery-Asperg Depression Rating Scale (MADRS) scores, respectively. Platelet 5-HT concentration was significantly lower in all depressed patients at baseline than in healthy subjects. Among patients, platelet 5-HT concentration or platelet MAO activity did not differ before treatment. There was no significant correlation between MADRS scores and peripheral biochemical markers. The limitation of the study was in a small number of patients, but its advantage was in a long-term (24 weeks) follow-up of both patients and healthy controls. Our results show that long-term sertraline treatment induced remission and response in 87% patients, decreased platelet 5-HT concentration after 4 and 24 weeks of treatment and decreased platelet MAO activity after 24 weeks and suggest that pretreatment values of platelet 5-HT and platelet MAO might not predict therapeutic outcome to sertraline treatment in female depressed patients.