Augmentative transcranial magnetic stimulation (TMS) combined with brain navigation in drug-resistant rapid cycling bipolar depression : a case report of acute and maintenance efficacy

The efficacy of transcranial magnetic stimulation (TMS) has been poorly investigated in the acute and maintenance treatment of bipolar depression. The present case supports the efficacy of low-frequency repetitive TMS (rTMS) of the right dorsolateral pre-frontal cortex (RDLPFC) combined to brain navigation in a drug-resistant, bipolar depressed subject with rapid cycling. While continuing the pharmacological treatment at stable doses, the patient was stimulated for 3 weeks at 1 Hz, 110% of motor threshold, 300 stimuli/day showing a significant improvement on the Hamilton Depression Rating Scale (HDRS(21)), the Montgomery-Asberg Depression Rating Scale (MADRS) and the Clinical Global Impression, improvement scale (CGI-I) total scores. On completion of the 3-week rTMS, the patient was treated with periodic maintenance sessions of rTMS at the same parameters of acute phase for an additional 6 months, at the end of which the therapeutic gains were maintained according to rating scales scores. Larger controlled trials assessing the acute and maintenance efficacy of rTMS in bipolar depression are needed

The Noradrenergic Action in Antidepressant Treatments : Pharmacological and Clinical Aspects

Even though noradrenaline has been recognized as one of the key neurotransmitters in the pathophysiology of major depression (MD), noradrenergic compounds have been less extensively utilized in clinical practice, compared to selective serotonin reuptake inhibitors (SSRIs). The development of the first selective noradrenergic reuptake inhibitor (NRI), Reboxetine, has not substantially changed the state of the art. In addition, Atomoxetine, a relatively pure NRI used for the treatment of ADHD, has shown mixed results when administered in augmentation to depressed subjects. Through a Medline search from 2000 to 2010, the present article provides an updated overview of the main pharmacological and clinical aspects of antidepressant classes that, partially or selectively, act on the noradrenergic systems. The noradrenergic action plays an important clinical effect in different antidepressant classes, as confirmed by the efficacy of dual action antidepressants such as the serotonin noradrenaline reuptake inhibitors (SNRIs), the noradrenergic and dopaminergic reuptake inhibitor (NDRI) Bupropion, and other compounds (e.g., Mianserin, Mirtazapine), which enhance the noradrenergic transmission. In addition, many tricyclics, such as Desipramine and Nortriptyline, have prevalent noradrenergic effect. Monoamine oxidase inhibitors (MAOIs), moreover, block the breakdown of serotonin, noradrenaline, dopamine and increase the availability of these monoamines. A novel class of antidepressantsthe triple reuptake inhibitorsis under development to selectively act on serotonin, noradrenaline, and dopamine. Finally, the antidepressant effect of the atypical antipsychotic Quetiapine, indicated for the treatment of bipolar depression, is likely to be related to the noradrenergic action of its metabolite Norquetiapine. Even though a pure noradrenergic action might not be sufficient to obtain a full antidepressant effect, a pronoradrenergic action represents an important element for increasing the efficacy of mixed action antidepressants. In particular, the noradrenergic action seemed to be related to the motor activity, attention, and arousal