Pramipexole in treatment-resistant depression: a 16-week naturalistic study

Lattanzi L, Dell'Osso L, Cassano P, Pini S, Rucci P, Houck PR, Gemignani A, Battistini G, Bassi A, Abelli M, Cassano GB. Pramipexole in treatment‐resistant depression: a 16‐week naturalistic study. Bipolar Disord 2002: 4: 307–314. © Blackwell Munksgaard 2002 Objective: To assess the antidepressant efficacy and tolerability of adjunctive pramipexole, a D₂–D₃ dopamine agonist, in patients with drug‐resistant depression. Methods: The study sample consisted of in‐patients with major depressive episode, according to the DSM‐IV, and drug resistance. Pramipexole was added to antidepressant treatment with TCA or SSRI, at increasing doses from 0.375 to 1.0 mg/day. Two independent response criteria were adopted: a >50% reduction of the Montgomery–Asberg Depressive Rating Scale (MADRS) total score and a score of 1 or 2 on the Clinical Global Impression scale (CGI‐I) at endpoint. Side‐effects were assessed by the Dosage Record Treatment Emergent Symptom Scale (DOTES). Results: Thirty‐seven patients were enrolled. Of these, 16 had unipolar depression and 21 had bipolar depression. Six patients dropped out in the first week. Of the 31 patients included in the analyses, 19 completed the 16‐week follow‐up. Mean maximal dose of pramipexole was 0.95 mg/day. Mean scores on MADRS decreased from 33.3 ± 8.4 at baseline to 13.9 ± 11.5 at endpoint (p < 0.001) and the CGI‐S decreased from 4.6 ± 0.8 at baseline to 2.8 ± 1.3 at endpoint (p < 0.001). At endpoint, 67.7% (21/31) of patients were responders on MADRS and 74.2% on CGI‐I. Of the 37 patients enrolled, 10 discontinued pramipexole because of adverse events. Conclusions: These preliminary data suggest that pramipexole adjunction to antidepressant treatment may be effective and well tolerated in patients with resistant major depression.     

The effectiveness of electroconvulsive therapy in treatment-resistant depression: a naturalistic study

OBJECTIVES: Electroconvulsive therapy (ECT) is a very effective treatment of major depressive disorder. However, its use has been declining over the years in the United Kingdom, where it is now reserved for cases where all other treatment options have failed. We wanted to assess whether ECT is still highly effective in such a severely treatment-resistant population. METHODS: We report results from an ongoing, prospectively conducted, naturalistic study examining the effectiveness of ECT at a general psychiatric hospital in Cardiff, United Kingdom. We present results on every patient who received ECT between March 2004 and August 2006 for major depressive episodes, had a baseline 24-item Hamilton Rating Scale for Depression (HRSD24) score of greater than or equal to 18 and consented for participation. RESULTS: We analyzed the results of 38 patients who had at least 6 ECT sessions or achieved remission earlier. They had spent on average 14.6 months in their current episodes and 6.2 years of their lifetime in depression. They had failed to respond to an average of 5.4 different pharmacological treatments. Twenty-five patients (65.8%) responded (improvement in HDRS24 of >or=50%) and 21 (53.3%) achieved remission (end point HDRS24 score or=60%). There was no correlation between the number of unsuccessful antidepressant trials and improvement (r = -0.04, P = 0.8). CONCLUSIONS: The ECT is still highly effective in severely treatment-resistant patients with major depressive disorder, with more than half of such patients achieving remission.     

Olanzapine for patients with treatment-resistant schizophrenia: a naturalistic case-series outcome study.

OBJECTIVE: This prospective, consecutive case-series outcome investigation evaluates the effectiveness of olanzapine in 16 patients with treatment-resistant schizophrenia. METHOD: Treatment resistance was defined as nonresponsiveness to at least 3 antipsychotic drugs from at least 2 different chemical classes. A minimum baseline score on the Brief Psychiatric Rating Scale (BPRS) of 45 was required for enrolment. Outcome evaluation measures included the BPRS, Global Assessment Scale (GAS), and Abnormal Involuntary Movement Scale (AIMS). RESULTS: Subjects (n = 16) has a mean age of 40 years and mean duration of illness of 16 years. Olanzapine treatment was initiated at 5 mg daily and was increased based on clinical judgement up to a maximum of 40 mg daily. Significant decreases in mean BPRS (P < 0.001) and GAS (P < 0.01) scores were observed at weeks 4, 8, 12, and 16, compared with baseline. Eight of 16 patients responded to olanzapine, as defined by a 20% decrease in BPRS score by week 16. Dyskinetic movements significantly increased at week 4 (P < 0.01) but did not differ from baseline at weeks 8 and 16. CONCLUSION: These results suggest that olanzapine at moderate to high doses may offer an effective treatment for a significant proportion of patients with schizophrenia nonresponsive to multiple trials of conventional antipsychotics. A randomized controlled trial is encouraged to validate these findings, and comparative trials are required to determine when clinicians should consider this approach.     

Management of patients with treatment-resistant depression

Treatment-resistant depression can be attributed to multiple causes, including nonadherence to medication and medical and psychiatric comorbidities. Selecting the appropriate strategy for a patient with treatment-resistant depression, whether it be a single antidepressant, a combination of medications, or a nonpharmacologic method, depends on a correct determination of the cause of the patient's resistance to treatment.     

Onset of improvement and response to mirtazapine in depression: a multicenter naturalistic study of 4771 patients

The purpose of this open multicenter study of 4771 patients with a DSM-IV diagnosis of Major Depressive Episode was to analyse the response to mirtazapine in general practice and primary care. Patients with a baseline score of at least 20 on the Montgomery-Asberg Depression Rating Scale (MADRS) were treated with mirtazapine for 6 weeks (30 mg/day) and clinically assessed by their psychiatrists at weekly intervals through the MADRS and Clinical Global Improvement (CGI) rating scales. The data analysis was carried out on an "intent-to-treat" basis to collect outcome information on all patients. Our results suggested that the efficacy of the antidepressant effect relates to a nonspecific process. Nearly all patients (95%) showed at least slight improvement at the end of the observation period, while the response to treatment was independent of the clinical forms of depression. In particular, all measures of efficacy displayed the maximum change within the first 2 weeks of treatment, with further improvement occurring at much slower rates. Significant improvement within the first 2 weeks of treatment was highly predictive of the final response, and can serve as a guideline for clinicians when deciding about increased dosage, augmentation, or change of medication in unresponsive patients. Detailed analyses of individual MADRS items showed that mirtazapine's pharmacological profile, unlike selective serotonin reuptake inhibitors, led relatively quickly to a significant reduction of suicidal thoughts, a fact of particular clinical relevance.     

Effects of 12 months of vagus nerve stimulation in treatment-resistant depression: a naturalistic study.

BACKGROUND: The need for effective, long-term treatment for recurrent or chronic, treatment-resistant depression is well established. METHODS: This naturalistic follow-up describes outpatients with nonpsychotic major depressive (n = 185) or bipolar (I or II) disorder, depressed phase (n = 20) who initially received 10 weeks of active (n = 110) or sham vagus nerve stimulation (VNS) (n = 95). The initial active group received another 9 months, while the initial sham group received 12 months of VNS. Participants received antidepressant treatments and VNS, both of which could be adjusted. RESULTS: The primary analysis (repeated measures linear regression) revealed a significant reduction in 24-item Hamilton Rating Scale for Depression (HRSD(24)) scores (average improvement, .45 points [SE = .05] per month (p < .001). At exit, HRSD(24) response rate was 27.2% (55/202); remission rate (HRSD(24) < or = 9) was 15.8% (32/202). Montgomery Asberg Depression Rating Scale (28.2% [57/202]) and Clinical Global Impression-Improvement (34.0% [68/200]) showed similar response rates. Voice alteration, dyspnea, and neck pain were the most frequently reported adverse events. CONCLUSIONS: These 1-year open trial data found VNS to be well tolerated, suggesting a potential long-term, growing benefit in treatment-resistant depression, albeit in the context of changes in depression treatments. Comparative long-term data are needed to determine whether these benefits can be attributed to VNS.     

Treating bipolar depression with esketamine: Safety and effectiveness data from a naturalistic multicentric study on esketamine in bipolar versus unipolar treatment-resistant depression

Background

Bipolar depression accounts for most of the disease duration in type I and type II bipolar disorder (BD), with few treatment options, often poorly tolerated. Many individuals do not respond to first-line therapeutic options, resulting in treatment-resistant bipolar depression (B-TRD). Esketamine, the S-enantiomer of ketamine, has recently been approved for treatment-resistant depression (TRD), but no data are available on its use in B-TRD.

Objectives

To compare the efficacy of esketamine in two samples of unipolar and bipolar TRD, providing preliminary indications of its effectiveness in B-TRD. Secondary outcomes included the evaluation of the safety and tolerability of esketamine in B-TRD, focusing on the average risk of an affective switch.

Methods

Thirty-five B-TRD subjects treated with esketamine nasal spray were enrolled and compared with 35 TRD patients. Anamnestic data and psychometric assessments (Montgomery-Asberg Depression Rating Scale/MADRS, Hamilton-depression scale/HAM-D, Hamilton-anxiety scale/HAM-A) were collected at baseline (T0), at one month (T1), and three months (T2) follow up.

Results

A significant reduction in depressive symptoms was found at T1 and T2 compared to T0, with no significant differences in response or remission rates between subjects with B-TRD and TRD. Esketamine showed a greater anxiolytic action in subjects with B-TRD than in those with TRD. Improvement in depressive symptoms was not associated with treatment-emergent affective switch.

Conclusions

Our results supported the effectiveness and tolerability of esketamine in a real-world population of subjects with B-TRD. The low risk of manic switch in B-TRD patients confirmed the safety of this treatment.     

Clozapine in treatment-resistant patients with schizophrenia,schizoaffective disorder,or psychotic bipolar disorder: a naturalistic 48-month follow-up study

BACKGROUND: The aim of this study was to evaluate the long-term efficacy and safety of clozapine in patients with treatment-resistant schizophrenia, schizoaffective disorder, or bipolar disorder with psychotic features. METHOD: 101 patients with a DSM-III-R diagnosis of schizophrenia (N = 34); schizoaffective disorder, bipolar type (N = 30); or bipolar disorder with psychotic features (N = 37) were naturalistically treated with clozapine at flexible doses over a 48-month period. Data were collected from 1994 to 2000. The Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impressions-Severity of Illness scale total predicted scores over time were estimated with random-effects regression models. Time to response to clozapine, defined as 50% reduction of BPRS score, was analyzed in the 3 diagnostic groups using the Kaplan-Meier method. Survival curves were compared using the log-rank test. RESULTS: The BPRS total predicted score halved its baseline value in 3 months for bipolar disorder patients, in 6 months for schizoaffective disorder patients, and in 24 months for schizophrenia patients. The proportion of subjects who satisfied the criterion for response to clozapine after 48 months of follow-up was significantly (p <.01) higher in the schizoaffective and bipolar disorder groups (90.0% and 83.8%, respectively) than in the schizophrenia group (64.7%). Baseline scores on the Global Assessment of Functioning (GAF) showed low levels of psychosocial and occupational functioning in all 3 groups. After 48 months of treatment, GAF scores showed a functional improvement in all 3 groups, with significantly (p <.01) greater improvement in the bipolar disorder group compared with the other groups. CONCLUSION: The findings of this study confirm the efficacy and safety of clozapine for treatment-resistant patients with a diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder with psychotic features. Patients with schizoaffective disorder and those with bipolar disorder show greater clinical improvement than those with schizophrenia. Patients with bipolar disorder have the shortest time to response and the highest psychosocial and occupational functioning levels. Patients with schizoaffective disorder have the lowest treatment discontinuation rate.     

Switching versus augmentation: a prospective, naturalistic comparison in depressed, treatment-resistant patients

OBJECTIVE: (1) To directly compare the effectiveness of switching antidepressants with augmenting them in depressed patients who do not respond to an initial adequate trial and (2) to determine whether there is a decreased likelihood of response to a second switch or augmentation trial in those patients who did not respond to the first intervention for treatment-resistant depression. METHOD: In a naturalistic, open-label design, all depressed outpatients (DSM-IV criteria) who were treatment resistant were prospectively assessed. Short- and long-term outcomes of switching versus augmentation were compared using the Clinical Global Impressions scale. RESULTS: In the acute phase, 37 (50.0%) of 74 subjects responded to 1 of the 2 interventions for treatment-resistant depression. Forty-five percent (N = 17) and 56% (N = 20) of the patients who had their antidepressant switched or augmented, respectively, responded to that intervention. Nearly three fourths (71.4%) of the acute responders maintained their response through 6 months of follow-up. In 18 patients who did not respond to the first switch or augmentation, 9 (50.0%) responded to a second trial. CONCLUSION: Switching antidepressants was somewhat less effective than augmentation, although this difference was not statistically significant. For patients who do not respond to an augmentation or switch, our results suggest that a second trial for treatment-resistant depression may be as effective as the first.     

奎硫平治疗难治性抑郁症的辅助作用

目的：探讨奎硫平治疗难治性抑郁症的增效作用及安全性。方法：58例难治性抑郁症患者分为研究组（抗抑郁药联合奎硫平治疗）和对照组（单用抗抑郁药治疗）各29例。观察6周。于治疗前及治疗1、2、4和6周采用汉密尔顿抑郁量表（HAMD）、汉密尔顿焦虑量表（HAMA）评定疗效;以治疗中出现的症状量表（TESS）评定不良反应。结果：两组治疗后HAMD和HAMA评分均较治疗前有显著降分（P〈0.05或P〈0.001）;以研究组HAMD减分率自治疗1周起、HAMA减分率自治疗4周起均显著高于对照组（P〈0.01或P〈0.001）。两组治疗各周TESS评分差异均无统计学意义（P〉0.05）。结论：奎硫平治疗难治性抑郁症增效作用明显且安全。     

难治性抑郁症患者血清胰岛素和神经内分泌激素的对照研究

目的研究难治性抑郁症患者治疗前后血清胰岛素和神经内分泌激素变化。方法难治性抑郁症患者(TRD组)、非难治性抑郁症患者(NTRD组)、健康者(正常对照组)各60例为研究对象,使用HAMD量表评估患者的临床症状,检测患者血清胰岛素、皮质醇(CORT)、促肾上腺皮质激素(ACTH)、三碘甲状腺原氨酸(T3)、游离三碘甲状腺原氨酸(FT3)、甲状腺素(T4)、游离甲状腺素(FT4)、促甲状腺激素刺激激素(TSH)等神经内分泌激素水平,并进行治疗前后各组上述指标的统计学处理。结果 TRD组血清胰岛素、CORT、ACTH、T3、FT3、T4、FT4、TSH与正常对照组存在显著差异,血清胰岛素、CORT、ACTH、FT4与NTRD组存在显著差异;NTRD组血清CORT、ACTH、T3、FT3、T4、FT4、TSH等与正常对照组存在显著差异(P0.05);治疗后,TRD组胰岛素、CORT、ACTH、FT3、FT4、TSH与对照组存在显著差异,而NTRD组CORT与对照组存在显著差异(P0.05)。结论 TRD患者HPA轴功能亢进、HPT轴功能低下等较NTRD患者更为严重,药物治疗后仍存在显著差异。     

Vagus nerve stimulation in 436 consecutive patients with treatment-resistant epilepsy: long-term outcomes and predictors of response

ObjectiveThe goal of this study was to assess the efficacy and safety of vagus nerve stimulation in a consecutive series of adults and children with treatment-resistant epilepsy (TRE).MethodsIn this retrospective review of a prospectively created database of 436 consecutive patients who underwent vagus nerve stimulator implantation for TRE between November 1997 and April 2008, there were 220 (50.5%) females and 216 (49.5%) males ranging in age from 1 to 76 years at the time of implantation (mean: 29.0 ± 16.5). Thirty-three patients (7.6%) in the primary implantation group had inadequate follow-up (< 3 months from implantation) and three patients had early device removal because of infection and were excluded from seizure control outcome analyses.ResultsDuration of vagus nerve stimulation treatment varied from 10 days to 11 years (mean: 4.94 years). Mean seizure frequency significantly improved following implantation (mean reduction: 55.8%, P < 0.0001). Seizure control ≥ 90% was achieved in 90 patients (22.5%), ≥ 75% seizure control in 162 patients (40.5%), ≥ 50% improvement in 255 patients (63.75%), and < 50% improvement in 145 patients (36.25%). Permanent injury to the vagus nerve occurred in 2.8% of patients.ConclusionVagus nerve stimulation is a safe and effective palliative treatment option for focal and generalized TRE in adults and children. When used in conjunction with a multidisciplinary and multimodality treatment regimen including aggressive antiepileptic drug regimens and epilepsy surgery when appropriate, more than 60% of patients with TRE experienced at least a 50% reduction in seizure burden. Good results were seen in patients with non-U.S. Food and Drug Administration-approved indications. Prospective, randomized trials are needed for patients with generalized epilepsies and for younger children to potentially expand the number of patients who may benefit from this palliative treatment.     

难治性抑郁症临床特征研究

目的:探讨难治性抑郁症患者的临床特征.方法:25例难治性抑郁症患者(难治组)和50例非难治性抑郁症患者(非难治组),进行一般情况评定,17项汉密尔顿抑郁量表(HAMD)、14项汉密尔顿焦虑量表(HAMA)量表评分,明尼苏达多项人格问卷(MMPI)评定.结果:难治组与非难治组比较,男性较多,受教育水平较低,发病年龄较早,...     

Bupropion SR in the naturalistic treatment of elderly patients with major depression

INTRODUCTION: Bupropion immediate release (IR) and bupropion sustained release (SR) are frequently used to treat geriatric depression, as they have few cardiovascular, gastrointestinal and sexual adverse effects. We sought to examine the efficacy and dosing patterns of bupropion in a naturalistic cohort of elderly subjects with major depression (MD). METHODS: 31 elderly ( > 60 years) patients with unipolar MD (DSM-IV) who were enrolled in Duke's Mental Health Clinical Research Center for the Study of Depression in Later Life were prescribed bupropion SR or IR, alone or in combination with other antidepressant agents, for 12 weeks. Montgomery-Asberg depression rating scale (MADRS) scores and clinical global impression (CGI) severity scores were used to define response. RESULTS: 74% (23/31) of the sample were responders (MADRS < 15) and 53% (16/30) achieved a partial (CGI = 2) or complete (CGI = 1) remission of MD at week 12. Among patients treated with bupropion SR monotherapy, the mean (range) maximal daily dose achieved was 240 mg (150-400 mg). Among those treated with bupropion IR, the mean (range) maximum daily dose achieved was 258 mg (150-450 mg). In subjects on monotherapy, 67% (10/15) of MD subjects were responders (MADRS < 15) and 50% (7/14) achieved full or partial remission. Response rates did not differ statistically among those with high and low medical comorbidity. CONCLUSIONS: In this naturalistic 12-week study, geriatric MD patients with high and low medical comorbidity responded well to bupropion and bupropion SR. In elderly patients, four to eight week acute treatment periods may be insufficient. Our findings suggest that nearly 50% of elderly depressed subjects at a tertiary center may need combination therapy over the course of their illness. Controlled randomized studies to establish the long-term efficacy and optimal dose of the newer antidepressants in geriatric depression are urgently needed.     

An open-label, rater-blinded, augmentation study of aripiprazole in treatment-resistant depression

Background: About 30% to 46% of patients with major depressive disorder (MDD) fail to fully respond to initial antidepressants. While treatment-resistant depression commonly refers to nonresponse or partial response to at least 2 adequate trials with antidepressants from different classes, due to variability in terminology, a staging system based on prior treatment response has been suggested. Aripiprazole is a novel atypical antipsychotic with partial agonism at dopamine D(2) and serotonin 5-HT(1A) receptors and antagonism at the 5-HT(2) receptors. The present study evaluated whether augmentation with aripiprazole would be beneficial and tolerable in patients with treatment-resistant MDD who had failed 1 or more trials of antidepressants. Method: In an open-label, rater-blinded study conducted from March 2003 through December 2003, 10 patients with DSM-IV MDD without psychotic features who had failed to respond to an adequate trial of at least 1 antidepressant were prescribed aripiprazole (10-30 mg/day) for 6 weeks. The dose of preexisting antidepressants remained unchanged. Treatment response was defined as a 50% or greater reduction in score on the Hamilton Rating Scale for Depression (HAM-D) from baseline to end of treatment. Secondary efficacy measures included scores on the Clinical Global Impressions-Improvement (CGI-I) and -Severity (CGI-S) scales. Results: Eight of 10 patients had failed 2 or more antidepressant trials. The mean daily dose of aripiprazole was 13.21 mg. Intent-to-treat analysis showed that mean ± SD HAM-D scores reduced significantly from baseline (23.0 ± 8.1) to end of treatment (8.1 ± 6.0) (p < .001). There was a significant reduction in CGI-I (p < .05) and a trend toward decrease in CGI-S (p = .06) score. Seventy percent of the subjects were responders and 30% achieved remission. Common adverse effects were akathisia (20%), nausea (20%), and restlessness (20%). Conclusions: The study indicates the potential utility of aripiprazole as an augmenting agent in treatment-resistant depression, particularly in those who had failed 2 or more antidepressant trials. Adequately powered, randomized controlled trials are necessary to evaluate the role of aripiprazole in treatment-resistant depression.     

Non-adherence with long-term prophylaxis: a 6-year naturalistic follow-up study of affectively ill patients

In a retrospective 6-year follow-up, we assessed the reasons for and the frequency and consequences of non-adherence in 76 affectively ill patients receiving lithium prophylaxis in two lithium clinics. Thirty-eight bipolar (50%), 21 unipolar (27.6%) and 17 schizoaffective patients (22.4%) diagnosed according to DSM-III-R, were investigated with a specialized follow-up documentation. Of the patients 53.9% discontinued prophylaxis at some time; 43.2% of the discontinuations occurred during the first 6 months. In contrast to other studies the main reason reported for non-adherence was resistance against long-term treatment. According to the Lithium Attitudes Questionnaire non-adherent patients showed significantly less acceptance of the prophylaxis in general, of the effectiveness of lithium and of the severity of their illness than adherent patients. In a multivariate analysis of various parameters, only the negative attitude to prophylaxis correlated significantly with non-adherence. Significant correlation was found between treatment outcome and duration of initial prophylaxis. During the 6-year follow-up only the adherent patients showed a significant reduction of the number and duration of admissions. Our findings confirmed non-adherence as a major problem in the effectiveness of lithium prophylaxis. The authors recommend prospective investigations of attitudes and the impact of psychoeducation on long-term adherence.     

Valproate augmentation in a subgroup of patients with treatment-resistant unipolar depression

Objectives: About 50% of patients with unipolar depression suffer from treatment-resistant depression (TRD). Animal studies have suggested potential antidepressant properties of valproate (VPA) possibly due to its implication in epigenetic programming. Methods: Fourteen TRD patients (seven males and seven females; age 19–59) received VPA (375–1000?mg/day) in addition to their treatment regimen after previously failing to respond to two or more antidepressant trials and/or different combinations. Clinical response to VPA was investigated prior the treatment (T-0) and after 1 (T-1), 4 (T-4) and 7 (T-7) months of therapy using the Montgomery–Asberg Depression Rating Scale (MADRS) and the Clinical Global Impression (CGI). Results: Compared to T-0, VPA significantly decreased MADRS score at T-1 (P?<?0.001), T-4 (P?<?0.001) and T-7 (P?<?0.001) (partial η²=0.86). Importantly, MADRS score at T-7 (13.6?±?1.6, mean?±?SEM) was closer to the reported value of remission (MADRS?<10), and none of the patients relapsed during the observational period. Compared to T-0, VPA also decreased CGI-Severity of illness score at T-1 (p?=?0.03), T-4 (p?<?0.001) and T-7 (p?<?0.001) (partial η²?=?0.74). Conclusions: Antidepressant augmentation with VPA provided substantial clinical improvement and maintenance over a relatively long-term period in a subgroup of patients with severe TRD. VPA thus deserves further exploration in large double-blind clinical trials.     

An open-label trial of riluzole in patients with treatment-resistant major depression

OBJECTIVE: This study was conducted to determine the efficacy and safety of riluzole, a glutamate-modulating agent, in patients with recurrent major depression. METHOD: After a 1-week drug-free period, subjects 18 years or older with a diagnosis of recurrent major depression and a Montgomery-Asberg Depression Rating Scale score > or = 20 received riluzole monotherapy (100-200 mg/day) openly for 6 weeks. RESULTS: Nineteen treatment-resistant depressed patients, 53% of whom were classified as having stage 2 treatment resistance or greater, received riluzole at a mean dose of 169 mg/day. Significant improvement occurred during weeks 3 through 6 for all patients and weeks 2 through 6 for completers. CONCLUSIONS: Although preliminary, these results indicate that riluzole may have antidepressant properties in some patients.