Utility of atypical antipsychotics in the treatment of resistant unipolar depression.
ABSTRACT Many patients fail to achieve an adequate response to antidepressant medication. Growing evidence suggests that atypical antipsychotics may augment antidepressant effects, resulting in a greater potential for response. Atypical antipsychotics possess pharmacological actions that are associated with antidepressant properties, including serotonin 5-HT(2) receptor antagonist and 5-HT(1A) and dopamine receptor partial agonist activity. In fact, the term 'atypical antipsychotic' is an unfortunate remnant of the early indication of these drugs in the treatment of schizophrenia. Soon after their introduction, the usefulness of atypical antipsychotics in bipolar disorder was firmly established and their use in the treatment of mood disorders has far outpaced their use in schizophrenia and other psychotic disorders. Aripiprazole has become the first agent to receive US FDA approval for the adjunctive treatment of unipolar depression. Most recently, Symbyax, a fluoxetine/olanzapine combination, received FDA approval for the acute treatment of treatment-resistant depression. This is the first medication to be FDA approved for this indication. In the present article, the usefulness of antipsychotics in the treatment of resistant unipolar depression is reviewed.
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ABSTRACT: Quetiapine is now used in the treatment of unipolar and bipolar disorders, both alone and in combination with other medications. In the current study, the sustained administration of quetiapine and N-Desalkyl quetiapine (NQuet) in rats in a 3 : 1 mixture (hQuetiapine (hQuet)) was used to mimic quetiapine exposure in patients because rats do not produce the latter important metabolite of quetiapine. Sustained administration of hQuet for 2 and 14 days, respectively, significantly enhanced the firing rate of norepinephrine (NE) neurons by blocking the cell body α₂-adrenergic autoreceptors on NE neurons, whether it was given alone or with a serotonin (5-HT) reuptake inhibitor. The 14-day regimen of hQuet enhanced the tonic activation of postsynaptic α₂- but not α₁-adrenergic receptors in the hippocampus. This increase in NE transmission was attributable to increased firing of NE neurons, the inhibition of NE reuptake by NQuet, and the attenuated function of terminal α₂-adrenergic receptors on NE terminals. Sustained administration of hQuet for 2 and 14 days, respectively, significantly inhibited the firing rate of 5-HT, whether it was given alone or with a 5-HT reuptake inhibitor, because of the blockade of excitatory α₁-adrenergic receptors on 5-HT neurons. Nevertheless, the 14-day regimen of hQuet enhanced the tonic activation of postsynaptic 5-HT(1A) receptors in the hippocampus. This increase in 5-HT transmission was attributable to the attenuated inhibitory function of the α₂-adrenergic receptors on 5-HT terminals and possibly to direct 5-HT(1A) receptor agonism by NQuet. The enhancement of NE and 5-HT transmission by hQuet may contribute to its antidepressant action in mood disorders.Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 02/2012; 37(7):1717-28. DOI:10.1038/npp.2012.18 · 7.83 Impact Factor
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ABSTRACT: Use of antidepressants is the gold standard therapy for major depression. However, despite the large number of commercially available antidepressant drugs there are several differences among them in efficacy, tolerability, and cost-effectiveness. In addition the optimal augmentation strategy is still not clear when dealing with treatment-resistant depression, a condition that affects 15% to 40% of depressed patients. We therefore reviewed the main characteristics of these drugs regarding their efficacy, tolerability, side effects and cost-effectiveness, by accessing all meta-analyses and systematic reviews published from 2004 to 2009. In addition, we reviewed the augmentation strategy of associated antidepressants with neurostimulation therapies (such as transcranial magnetic stimulation [TMS] and transcranial direct current stimulation [tDCS]). A search was undertaken in MEDLINE, Web of Science, Cochrane, and Scielo databases. We included: 21 meta-analyses of antidepressant trials, 15 neurostimulation clinical trials and 8 studies of pharmacoeconomics. We then performed a comprehensive review on these articles. Although recent meta-analyses suggest sertraline and escitalopram might have increased efficacy/tolerability, other studies and large pragmatic trials have not found these to be superior to other antidepressant drugs. Also, we did not identify any superior drug in terms of cost-effectiveness due to the different designs observed among pharmacoecomics studies. Side effects such as sexual dysfunction, gastrointestinal problems and weight gain were common causes of discontinuation. Tolerability was an important issue for novel neurostimulation interventions, such as TMS and tDCS. These therapies might be interesting augmentation strategies, considering their benign profile of side effects, if proper safety parameters are adopted.Therapeutics and Clinical Risk Management 11/2009; 5:897-910. DOI:10.2147/TCRM.S5751 · 1.47 Impact Factor
- Quaderni Italiani di Psychiatria 12/2009; 28(4):135-137. DOI:10.1016/j.quip.2009.11.001