Risperidone augmentation of selective serotonin reuptake inhibitors in major depression.
ABSTRACT At low doses, risperidone acts as a 5-HT2 antagonist. Preclinical data suggest 5-HT2 antagonists may enhance the action of serotonin. This report examines the clinical use of risperidone to augment selective serotonin reuptake inhibitor (SSRI) anti-depressants in patients who have not responded to SSRI therapy.
In 8 patients with major depressive disorder without psychotic features (DSM-IV) who had not responded to an SSRI, risperidone was added to the ongoing SSRI treatment. Hamilton Rating Scale for Depression scores were obtained before and after the addition of risperidone.
These 8 patients remitted within 1 week of the addition of risperidone. Risperidone also appeared to have beneficial effects on sleep disturbance and sexual dysfunction.
Risperidone may be a useful adjunct to SSRIs in the treatment of depression.
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ABSTRACT: Patients (30-50%) with non-psychotic major depression will not respond despite an adequate trial of antidepressant medication. This study evaluated risperidone as an augmenting agent for patients who failed or only partially responded to an adequate trial of an antidepressant medication. Ninety-seven patients with unipolar non-psychotic major depression who were not responsive to antidepressant monotherapy were randomized to risperidone (0.5-3mg/day) or placebo augmentation in a four-week, double-blind, placebo controlled treatment trial. The primary outcome measure was remission defined by a score of < or =10 on the Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes measures were the Hamilton Rating Scale for Depression, the Clinician Global Impression of Severity scale and the overall satisfaction item of the Quality of Life and Enjoyment Questionnaire. Subjects in both treatment groups improved significantly over time. The odds of remitting were significantly better for patients in the risperidone vs. placebo arm (OR=3.33, p=.011). At the end of 4 weeks of treatment 52% of the risperidone augmentation group remitted (MADRS< or =10) compared to 24% of the placebo augmentation group (CMH(1)=6.48, p=.011), but the two groups were converging. Patients in the risperidone group also reported significantly more improvement in quality-of-life than patients in the placebo group. There were no between-group differences in the number of adverse events reported, however, weight gain was significantly higher in the group receiving risperidone. Augmentation of an antidepressant with risperidone for patients with difficult-to-treat depression leads to more rapid response and a higher remission rate and better quality-of-life.Journal of Psychiatric Research 07/2008; 43(3):205-14. DOI:10.1016/j.jpsychires.2008.05.003 · 4.09 Impact Factor
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ABSTRACT: The role of atypical antipsychotics as add-on treatments and as primary mood stabilizers in different phases of bipolar disorder is an important current research area. Although in bipolar patients the main therapeutic indication of quetiapine (QTP) is the management of acute mania, several observations suggest that this agent may exert antidepressant as well as antimanic effects. However, in our knowledge, there are no preclinical studies supporting this hypothesis. Thus, the main goal of the present work was to evaluate the putative antidepressant effect of QTP (0.4, 2.0, or 10 mg/kg/day), in comparison to amitriptyline (AMI) (2 or 5 mg/kg/day), in rats exposed to acute or chronic stress. The administration of QTP, 2 mg/kg/day, prevents the onset of anhedonia in rats exposed to a 6-week chronic mild stress (CMS) protocol. The effect of QTP has a slow onset, beginning at week 5, and causes a complete recovery from anhedonia. In this respect, the effect of QTP is similar to that obtained after chronic administration of AMI 2 or 5 mg/kg/day. Our findings also indicate that a 6-week administration of QTP, 2 or 10 mg/kg/day, has protective effects against the onset of anhedonia caused by the exposure to an acute subthreshold stressful event in rats that have previously experienced the CMS procedure. The results suggest that QTP is able to prevent both the transient mood depression caused by acute stress and the long-lasting anhedonic state induced by exposure, over a period of weeks, to a variety of unpredictable mild stressors.Neuropsychopharmacology 09/2007; 32(8):1783-90. DOI:10.1038/sj.npp.1301291 · 7.83 Impact Factor
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ABSTRACT: There is preliminary evidence that the atypical antipsychotic aripiprazole, which is a partial agonist at D(2) and 5-HT(1A) receptors and a potent antagonist at 5-HT(2A) receptors, may be useful as an augmentation strategy in treatment-resistant depression. In this 4-week open-label non-randomized parallel-group study, the safety and efficacy of aripiprazole as add-on treatment strategy in patients suffering from non-delusional depression was investigated. Forty drug-free depressed inpatients without psychotic symptoms (13 men, 27 women), suffering from a major depressive episode or bipolar disorder, depressive state (DSM-IV criteria), were included in the study. The patients were treated either with mirtazapine monotherapy (45 mg/day) or combination therapy (mirtazapine 45 mg/day plus aripiprazole 15 mg/day) for 4 weeks. Safety and efficacy were assessed weekly using the Hamilton Depression Rating Scale, the Simpson-Angus Scale and the Barnes Akathisia Scale. Mirtazapine monotherapy and combined treatment with mirtazapine and aripiprazole showed comparable antidepressant effects as assessed at the endpoint of the study period. However, additional administration of aripiprazole accelerated the onset of antidepressant action in patients suffering from treatment-resistant depression. Additive use of aripiprazole reduced the mirtazapine-induced increase in the body mass index. Moreover, mirtazapine had favourable effects on aripiprazole-induced akathisia. No other extrapyramidal side effects were seen in the combination therapy group. Combined therapy with mirtazapine and aripiprazole is a safe and well-tolerated treatment option which may be useful especially in treatment-resistant depression. Double-blind controlled studies are needed to further explore the efficacy and safety of aripiprazole in depressed patients.The World Journal of Biological Psychiatry 02/2007; 8(2):112-22. DOI:10.1080/15622970601136203 · 4.23 Impact Factor