Risperidone Augmentation of Selective Serotonin Reuptake Inhibitors in Major Depression

Department of Psychiatry, Yale University, New Haven, Connecticut, United States
The Journal of Clinical Psychiatry (Impact Factor: 5.5). 05/1999; 60(4):256-9. DOI: 10.4088/JCP.v60n0410
Source: PubMed


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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    • "Atypical antipsychotics (e.g., aripiprazole, olanzapine, 20 quetiapine, risperidone, ziprasidone) belong to the agents that are 21 expected to potentiate the efficacy of ADs [1,4–6]. Several clinical 22 reports have postulated a beneficial effect of an additional low dose 23 risperidone to ongoing treatment with ADs (in particular, selective 24 serotonin reuptake inhibitors (SSRI), such as fluoxetine, fluvox- 25 amine or paroxetine [7] [8] [9] [10] [11]. Like other atypical antipsychotic 26 drugs, risperidone is known to produce minimal extrapyramidal 27 side-effects compared to classical antipsychotics (e.g., chlorprom- 28 azine) [12]. "
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    ABSTRACT: Background The aim of our study was to understand the mechanism of clinical efficacy of the combination of an antidepressant and risperidone in drug-resistant depression. Methods We studied the effect of an antidepressant (mirtazapine) and risperidone (atypical antipsychotic), given separately or jointly on extracellular levels of dopamine (DA), serotonin (5-HT) and noradrenaline (NA) in the rat frontal cortex. The animals were given a single intraperitoneal injection of risperidone (1 mg/kg) and mirtazapine (10 and 20 mg/kg). The release of monoamines in the rat frontal cortex was investigated using a microdialysis in freely moving animals, and monoamine levels were assayed by HPLC with coulochemical detection. Results Risperidone increased the cortical extracellular levels of DA, 5-HT and NA. Similarly, mirtazapine dose-dependently increased the cortical extracellular levels of the monoamines studied. A combination of mirtazapine either at the higher dose (20 mg/kg) or at both doses (10 and 20 mg/kg) with risperidone produced a significant effect on DA and NA release, respectively compared to the effect of any drug given alone. The increase in the DA (but not NA) release induced by mirtazapine plus risperidone was partly blocked by the selective 5-HT1A antagonist WAY 100635 (0.2 mg/kg). Conclusions Our data indicate that the increase of cortical extracellular levels of DA and NA by combined administration of mirtazapine and risperidone may be of crucial importance to the pharmacotherapy of drug resistant depression, and that, among other mechanisms, 5-HT1A, 5-HT2A, α2-adrenergic and histamine H1 receptors may play some role in this effect.
    Full-text · Article · Dec 2014 · Pharmacological reports: PR
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    • "In depressed patients, adaptive upregulation of postsynaptic receptors, such as the serotonergic 2A (5-HT2A) receptor, has been observed (Cahir et al., 2007; Shelton et al., 2009). Furthermore, 5-HT2A receptor expression has been shown to be altered after SSRI treatment in humans and dogs (Gray and Roth, 2001; Peremans et al., 2005) and atypical antipsychotics with 5-HT2A receptor antagonist properties have been shown to augment the therapeutic effect of SSRIs (Marek et al., 2003; Nelson and Papakostas, 2009; Ostroff and Nelson, 1999; Philip et al., 2008). Therefore , the postsynaptic 5-HT2A receptor is thought to be a possible target for antidepressant therapy. "
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    ABSTRACT: Down-stream neuronal alterations, including changes in the 5-HT-2A receptor system, play an important role in the etiology and treatment of depression. The present study examined the effect of prolonged opioid treatment on cerebral 5-HT2A receptors. Cerebral 5-HT2A receptor availability was estimated in seven healthy five-year-old female neutered Beagle dogs pre and post 10-day morphine treatment (oral sustained release morphine 20 mg twice daily for ten days) with 123I-R-91150, a 5-HT2A selective radioligand, and SPECT. 5-HT2A receptor binding indices (BI) for the frontal, parietal, temporal and occipital cortex and the subcortical region were calculated. Statistical analysis was performed using a linear mixed-effect model with treatment as fixed effect and dog as random effect. Morphine treatment significantly (p≤0.05) lowered 5-HT2A BIs in the right and left frontal cortex, the right and left temporal cortex, the right and left parietal cortex, and the subcortical region. The decreased cerebral 5-HT2A receptor availability following prolonged morphine exposure provides further evidence for an interaction between the opioid and serotonergic system.
    Full-text · Article · Jul 2014 · European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology
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    • "The results of this trial suggested that the therapeutic effect of haloperidol and amitriptyline augmentation was superior to risperidone, in the total group of patients with combined psychotic and depressive symptoms.35 However, more recent studies demonstrated robust efficacy and tolerability when risperidone was used to augment SSRI antidepressants for the acute treatment of patients suffering from both psychotic and nonpsychotic major depressive episodes.36,37 "
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    ABSTRACT: The purpose of this study was to compare the effectiveness of novel antipsychotics in the treatment of psychotic depression. Consecutive patients who were admitted (n = 51) with a confirmed diagnosis of major depression with psychotic features (delusions or hallucinations or both) participated in this open-label, naturalistic study. All patients were treated with selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) (citalopram or venlafaxine extended release [XR]), and atypical antipsychotic agents were added, as tolerated, during the first week of initiating the citalopram or venlafaxine. There were patients (n = 16) who received risperidone, who received quetiapine (n = 20), and who received olanzapine (n = 15), as an adjunctive treatment to either citalopram or venlafaxine for at least 8 weeks. Outcome measures included the Clinical Global Impression-Severity subscale (CGI-S), as the primary outcome measure, as well as the Hamilton Rating Scale for Depression-21 item (HAM-D21) and the Brief Psychiatric Rating Scale (BPRS). Tolerance to treatments and weight changes were monitored over the period of the trial. All patients completed the trial with no drop outs. At 8 weeks, there was a statistically significant (P < 0.001) clinical improvement in all outcome measures for both the depressive and psychotic symptoms, for all three groups of atypical adjunctive treatments. Utilizing analysis of variance (ANOVA), there were no significant differences between the three adjunctive treatment groups in outcome measures. The three antipsychotic agents were equally tolerated. At 8 weeks there was slight increase in weight in the three treatment groups, which was statistically significant (P > .01) in the olanzapine group. Quetiapine, risperidone, and olanzapine, given as adjunctive treatment with SSRIS or SNRIs can significantly and equally improve depressive and psychotic symptoms, in the short-term treatment of major depression with psychotic features. The author recommends that large controlled trials be conducted to examine the differences in long-term efficacy and tolerance between the atypical antipsychotic agents, in the treatment of major depression with or without psychotic features.
    Full-text · Article · Apr 2013 · Neuropsychiatric Disease and Treatment
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