_______________________________________________________________________ Depression and Suicide
Transcranial Magnetic Stimulation Repetitive transcranial magnetic stimulation delivers high- intensity magnetic pulses to the cortex through a stimulating coil placed to the forehead [299; 300]. It is a first-line MDD treatment in patients with one or more failed antidepressant trial [282]. Efficacy in treatment-resistant depression was estab- lished using stringent criteria; analysis of 23 trials found signifi- cantly greater efficacy and effect size for repetitive transcranial magnetic stimulation over sham [301]. In randomized clinical trials, 20 to 30 sessions over four or more weeks achieved 40% to 55% response and 25% to 35% remission rates [302]. The most frequent side effects are transient scalp pain (40%) and headache (30%). Both diminish with repeated treatment and respond to over-the-counter analgesics. The cognitive safety profile is benign. Seizures are the most serious side effect, but fewer than 25 cases have been reported worldwide [282; 303]. Repetitive transcranial magnetic stimulation is contraindicated in patients with any metal or metallic hardware in the head (except the mouth), with a history of seizures, and who take medications that lower seizure threshold [282; 304]. Transcranial Direct-Current Stimulation A sham-controlled trial randomized patients with MDD to escitalopram (20 mg/day) or prefrontal transcranial direct- current stimulation for 10 weeks. With mean decrease in HAM-D score from baseline, both treatment groups were superior to placebo, but transcranial direct-current stimulation was inferior to escitalopram. New-onset manic switch during transcranial direct-current stimulation therapy is a concerning adverse event; however, the number of reported cases is low [283; 305; 306]. Magnetic Seizure Therapy Magnetic seizure therapy uses focused brain stimulation (generally of the right frontal area) to induce a focal seizure. It intends to produce the efficacy of ECT without the cognitive side effects by sparing the hippocampus from seizure activity [21]. A meta-analysis of 1,092 patients with treatment-resistant depression found response and remission rates for active vs. sham magnetic seizure therapy of 25% and 17%, versus 9% and 6%, respectively [307]. A 2016 meta-analysis found that while magnetic seizure therapy had a small short-term effect in improving depression compared with sham, follow-up studies did not demonstrate that the small effect would con- tinue for longer periods [308]. A study of 23 patients with treatment-resistant depression found that 44.4% of the group experienced resolution of suicidal ideation following magnetic seizure therapy [309]. Magnetic seizure therapy add-on to SSRI treatment in treatment-resistant depression improves outcome, but more data is needed before it can be considered a first-line therapy for treatment-resistant depression [307; 310].
Pharmacotherapies Ketamine
Ketamine is an N- methyl-D-aspartate receptor (NMDA-R) antagonist that was approved for use as an anesthetic in 1970. Demonstration that a single IV dose in patients with treatment-resistant depression reliably produced rapid, robust antidepressant effects for one week was a breakthrough discov- ery for research and a turning point for patients for whom all other treatment approaches had failed [311]. The short-term efficacy of ketamine treatment of refractory MDD and bipolar depression is now established; over a dozen placebo-controlled trials have shown that patients with refractory MDD or bipolar depression have significantly greater response, remission, and depressive symptom reduction to single-dose IV ketamine than placebo from 40 minutes through days 10 to 12 post-treatment [312; 313]. The approach has become standardized, using a sub-anesthetic dose: 0.5 mg/kg IV over a 40-minute infusion. In a 2015 analysis, ketamine was designated as one of two psychiatric treatments that had the highest potential impact on patient outcomes. This designation was based on the seri- ous unmet need for fast-acting, well-tolerated antidepressants with efficacy in refractory MDD and bipolar depression [47]. Substantial interest and optimism among patients, families, patient advocacy groups, and clinicians has been generated by clinical reports of unique antidepressant effects with ketamine and frequent media coverage of potential ketamine treatment benefits. Demand for clinical access to ketamine treatment is rapidly escalating, and a growing number of clinics and practi- tioners are now offering various forms of ketamine treatment for mood and anxiety disorders throughout the United States [314]. However, many in the field suggest greater caution, and concerns that enthusiasm and desperation of patients and families may be leading to ketamine used in ways that are not yet supported by existing evidence. Others note the lack of large-scale or long-term studies of ketamine treatment in refrac- tory MDD [314]. Use of IV ketamine for treatment-resistant depression is off-label, whereas an intranasal formulation (esketamine) is FDA-approved for treatment-resistant depres- sion and for MDD with suicidality, when used in conjunction with an oral antidepressant [64; 175]. A systematic review and meta-analysis of five randomized controlled trials found that twice-weekly dosing of esketamine as augmentation to ongo- ing oral antidepressant use compared with placebo improved depressive symptoms and remission in patients with MDD at up to 28 days follow-up [315]. Rapastinel Rapastinel is an investigational NMDA-R partial agonist with robust cognitive enhancement and rapid, long-lasting antide- pressant effects. This drug comes as a pre-filled IV syringe, administered in less than one minute. After one injection, therapeutic effects appear within two hours and last up to seven days. Rapastinel is well-tolerated, and antidepressant
199
EliteLearning.com/Psychology
Powered by FlippingBook