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.
SourceAvailable from: Giuseppe Di Giovanni[Show abstract] [Hide abstract]
ABSTRACT: 5-Hydroxytryptamine 2A receptors (5-HT2A-Rs) are G-protein coupled receptors. In agreement with their location in the brain, they have been implicated not only in various central physiological functions including memory, sleep, nociception, eating and reward behaviors, but also in many neuropsychiatric disorders. Interestingly, a bidirectional link between depression and epilepsy is suspected since patients with depression and especially suicide attempters have an increased seizure risk, while a significant percentage of epileptic patients suffer from depression. Such epidemiological data led us to hypothesize that both pathologies may share common anatomical and neurobiological alteration of the 5-HT2A signaling. After a brief presentation of the pharmacological properties of the 5-HT2A-Rs, this review illustrates how these receptors may directly or indirectly control neuronal excitability in most networks involved in depression and epilepsy through interactions with the monoaminergic, GABAergic and glutamatergic neurotransmissions. It also synthetizes the preclinical and clinical evidence demonstrating the role of these receptors in antidepressant and antiepileptic responses.Frontiers in Pharmacology 01/2015; 6:46. DOI:10.3389/fphar.2015.00046
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ABSTRACT: As many as 30% of individuals diagnosed with depression are nonresponsive to traditional antidepressant medication. Augmentation and combination strategies have emerged in an attempt to address this issue. Atypical antipsychotics (e.g., olanzapine), when added to a selective serotonin reuptake inhibitor (e.g., fluoxetine) have shown great promise in the treatment of these treatment-resistant patients. As of yet, the precise neural mechanisms responsible for the beneficial clinical effect of these combinations are not completely understood.Methods Separate groups of rats received either saline or fluoxetine (10 mg/kg/day) for 24 hours or 3 weeks via subcutaneously implanted osmotic pumps. The effects of either intravenous saline or olanzapine (.3, 1.0, or 3.0 mg/kg) on locus coeruleus (LC) neuronal activity were then assessed via extracellular single-unit recordings.ResultsAcute administration of olanzapine produced a significant elevation of the firing rate and burst firing of LC cells, and chronic, but not acute, administration of fluoxetine decreased baseline and burst firing of LC cells; however, when given in combination, an interaction of fluoxetine and olanzapine was observed, with olanzapine causing a significantly greater increase in LC firing rate and burst firing after acute and chronic administration of fluoxetine.Conclusions These results provide a potential neural mechanism for the beneficial clinical effects of the olanzapine/fluoxetine combination. The increase in baseline and burst firing of LC neurons in the groups receiving both fluoxetine and olanzapine would result in enhanced norepinephrine release in projection areas (e.g., prefrontal cortex), which could lead to a reduction in depressive symptoms.Biological Psychiatry 06/2004; 55(11):1103-1109. DOI:10.1016/S0006-3223(04)00213-6 · 9.47 Impact Factor
Article: Combining antidepressants.[Show abstract] [Hide abstract]
ABSTRACT: Treatment-resistant depression is a common problem encountered by psychiatrists. These patients are often difficult to treat effectively. Strategies for addressing patients with treatment-resistant depression include changing medications, adding another antidepressant (antidepressant polypharmacy), and augmenting treatment with a non-antidepressant.