The following case illustrates the benefits of levomilnacipran in a depressed patient who suffers from chronic pain and impaired social function.
CASE Mrs. C, age 44, was referred by her outpatient psychologist and her primary care provider for management of refractory depression. She did not respond to an SSRI, an SNRI, or augmentation with bupropion and aripiprazole.
Mrs. C was on disability leave from work because of depression and cervical spine pain that might have been related to repetitive movement as a telephone customer service representative. She complained of loss of motivation, fatigue, and high anxiety about returning to work because of the many unhappy customers she felt she had to soothe.
Levomilnacipran was started at 20 mg/d for 2 days, then titrated to 40 mg/d for 5 days, 80 mg/d for 1 week, and 120 mg/d thereafter. Her previous antidepressants, fluoxetine and bupropion, were discontinued while levomilnacipran was titrated.
Mrs. C continued to receive weekly psychotherapy and physical therapy and to take tizanidine, a muscle relaxant, and over-the-counter medications for pain. Her Patient Health Questionnaire (PHQ-9) score declined from 13 when levomilnacipran was started to 5 at the next visit, 6 weeks later.
Within 4 months of initiating levomilnacipran, Mrs. C returned to work with a series of cue cards to use when speaking with irate or unhappy customers. At that point, her cervical spine pain was barely noticeable and no longer interfered with function.
Vortioxetine
This agent has a novel multimodal mechanism of action (Table 3). It is an SSRI as well as a 5-HT1A full agonist and 5-HT3 receptor antagonist. Vortioxetine also has an inhibitory effect on 5-HT7 and 5-HT1D receptors and partial agonism of 5-HT1B receptors.
The downstream effect of this multimodal action is an increase in dopamine, norepinephrine, and acetylcholine activity in the prefrontal cortex.10 These downstream effects are thought to help restore some cognitive deficits associated with depression.11
Vortioxetine is the only antidepressant among the 3 discussed in this article that was studied over a long period to ensure that short-term benefits continue beyond the 6- to 8-week acute Phase-III studies. A high remission rate (61%) was observed in patients who were treated on an open-label basis with vortioxetine, 10 mg/d, then randomized to maintenance with vortioxetine or placebo.12
Older patients. Vortioxetine is unique among these 3 antidepressants in that it is the only one studied separately in geriatric patients: In an 8-week Phase-III trial, 452 geriatric patients age 64 to 88 were randomized to 5 mg/d of vortioxetine or placebo.13 Vortioxetine was significantly more effective than placebo at Week 6.
Vortioxetine also is the only antidepressant investigated for an effect on cognitive deficits: In a Phase-III double-blind, placebo-controlled study of 602 patients with major depressive disorder, using duloxetine as active reference, vortioxetine was found to have a significant effect on Digit Symbol Substitution Test scores, compared with placebo, independent of its antidepressant effect (ie, patients who did not show any antidepressant benefit still showed an improvement in attention, speed processing, memory, and executive function).14
We have found, therefore, that vortioxetine is helpful for depressed patients who have cognitive deficits, especially geriatric patients.
CASE Mrs. B, age 84, married, has a 4-year history of depression. She has taken several antidepressants with little consistent relief.
A brief psychiatric hospitalization 2 years ago temporarily reduced the severity of Mrs. B’s depression; gradually, she relapsed. She felt hopeless and resisted another psychiatric evaluation. Mrs. B’s family includes several clinicians, who wondered if she was developing cognitive deficits that were interfering with her recovery.
At initial evaluation, Mrs. B failed to recall 2 of 3 objects but performed the clock drawing test perfectly—qualifying her for a diagnosis of mild cognitive impairment in addition to major depression. Her PHQ-9 score at baseline was 22.
On the assumption that the severity of her depression was contributing to cognitive deficits, vortioxetine, 5 mg/d, was initiated for 2 weeks and then titrated to 10 mg/d.
At 4 weeks’ follow-up, Mrs. B passed the Mini-Cog test; her PHQ-9 score fell to 8. She has remained asymptomatic for 6 months at the 10-mg/d dosage; her lowest PHQ-9 score was 5.
Adverse effects. The most common adverse effects are mild or moderate GI in nature. Weight gain and adverse sexual effects were not significantly different among patients receiving vortioxetine than among patients given placebo.
A note about the safety of these agents
All 3 of these antidepressants carry the standard black-box warning about the elevated risk of suicide in patients taking an antidepressant. None of them are approved for patients age <18.
Continue to: Suicidal ideation was reported