Prescriber's Guide to Using 3 New Antidepressants W

VILAZODONE • LEVOMILNACIPRAN • VORTIOXETINE Prescriber’s guide to using 3 new antidepressants How do they work? What makes them different? And which patients might benefit most from taking them? Ahmed Z. Elmaadawi, MD Narendra Singh, MD ith a prevalence >17%, depression is one of the most common Jagadeesh Reddy, MD, MPH mental disorders in the United States and the second leading Adjunct Clinical Assistant Professors W 1,2 cause of disability worldwide. For decades, primary care and mental Suhayl Joseph Nasr, MD health providers have used selective serotonin reuptake inhibitors (SSRIs) Volunteer Clinical Professor as first-line treatment for depression—yet the remission rate after the first Department of Psychiatry trial of an antidepressant is <30%, and continues to decline after a first Indiana University School of Medicine- antidepressant failure.3 South Bend Campus South Bend, Indiana That is why clinicians continue to seek effective treatments for depression—ones that will provide quick and sustainable remission—and why Disclosures Drs. Elmaadawi, Singh, and Reddy report no financial scientists and pharmaceutical manufacturers have been competing to relationships with any company whose products develop more effective antidepressant medications. are mentioned in this article or with manufacturers of competing products. Dr. Nasr is a member of the In the past 4 years, the FDA has approved 3 antidepressants— speakers’ bureau for Forest Pharmaceuticals and Takeda vilazodone, levomilnacipran, and vortioxetine—with the hope of Pharmaceutical Company Limited and H. Lundbeck A/S. increasing options for patients who suffer from major depression. These 3 antidepressants differ in their mechanisms of action from other available antidepressants, and all have been shown to have acceptable safety and tolerability profiles. In this article, we review these novel antidepressants and present some clinical pearls for their use. We also present our observations that each agent appears to show particular advantage in a certain subpopulation of depressed patients who often do not respond, or who do not adequately respond, to other antidepressants. continued on page 32 MATT MATT MANLEY FOR CURRENT PSYCHIATRY Current Psychiatry Vol. 14, No. 2 29 continued from page 29 Table 1 The following case—a patient with depression, significant anxiety, and IBS— Fast facts: Vilazodone exemplifies the type of patient for whom we Brand name Viibryd find vilazodone most useful. Class Serotonin reuptake inhibitor and 5-HT1A receptor partial CASE Ms. A, age 19, is a college student with agonist a history of major depressive disorder, social FDA approval January 24, 2011 anxiety, and panic attacks for 2 years and IBS Novel date antidepressants for 3 years. She was taking lubiprostone for Manufacturer Forest Laboratories, Inc. IBS, with incomplete relief of GI symptoms. Dosage forms 10 mg, 20 mg, and 40 mg tablets Because the family history included depression in Ms. A’s mother and sister, and both Starting 10 mg/d dosage were doing well on escitalopram, we began Target dosage 40 mg/d a trial of that drug, 10 mg/d, that was quickly titrated to 20 mg/d. Ms. A did not respond to 20 mg of escitalo- Clinical Point pram combined with psychotherapy. The unique Vilazodone We then started vilazodone, 10 mg/d after Vilazodone was approved by the FDA in breakfast, for the first week, and reduced escital- presynaptic 5-HT1A 2011 (Table 1). The drug increases serotonin opram to 10 mg/d. During Week 2, escitalopram partial agonism of bioavailability in synapses through a strong was discontinued and vilazodone was increased vilazodone is similar dual action: to 20 mg/d. During Week 3, vilazodone was to that of buspirone: • blocking serotonin reuptake through titrated to 40 mg/d. the serotonin transporter Ms. A tolerated vilazodone well. Her depressive Both drugs initially • partial agonism of the 5-HT1A presyn- symptoms improved at the end of Week 2. inhibit serotonin aptic receptor. Unlike her experience with escitalopram, synthesis and Vilazodone also has a moderate effect on Ms. A’s anxiety symptoms—tenseness, racing neuronal firing the 5-HT4 receptor and on dopamine and thoughts, and panic attacks—all diminished norepinephrine uptake inhibition. when she switched to vilazodone. Notably, her The unique presynaptic 5-HT1A partial IBS symptoms also were relieved, and she dis- agonism of vilazodone is similar to that of continued lubiprostone. buspirone, in which both drugs initially Ms. A’s depression remained in remission inhibit serotonin synthesis and neuronal for 2 years, except for a brief period one sum- firing.4 Researchers therefore expected that mer, when she thought she “could do without vilazodone would be more suitable for any medication.” She tapered the vilazodone, patients who have depression and a comor- week by week, to 10 mg/d, but her anxiety and bid anxiety disorder; current FDA approval, bowel symptoms resurfaced to a degree that she however, is for depression only. resumed the 40-mg/d dosage. Adverse effects. The 5-HT4 receptor on which vilazodone acts is present in the gas- Levomilnacipran trointestinal (GI) tract, and contributes to This drug is a 2013 addition to the small regulating symptoms in patients with irri- serotonin–norepinephrine reuptake inhibi- table bowel syndrome (IBS)5; not surpris- tor (SNRI) family of venlafaxine, des- ingly, the most frequent adverse effects of venlafaxine, and duloxetine7 (Table 2). Discuss this article at vilazodone are GI in nature (diarrhea, nau- Levomilnacipran is the enantiomer of mil- www.facebook.com/ sea, vomiting). nacipran, approved in Europe for depres- CurrentPsychiatry Headache is the most common non- sion but only for fibromyalgia pain and GI side effect of vilazodone. Depressed peripheral neuropathy in the United States.8 patients who took vilazodone had no sig- (Levomilnacipran is not FDA-approved for nificant weight gain and did not report treating fibromyalgia pain.) adverse sexual effects, compared with sub- Levomilnacipran is unique because it Current Psychiatry 32 February 2015 jects given placebo.6 is more of an NSRI, so to speak, than an SNRI: That is, the drug’s uptake inhibition Table 2 of norepinephrine is more potent than its serotonin inhibition. Theoretically, Fast facts: Levomilnacipran levomilnacipran should help improve Brand name Fetzima cognitive functions linked to the action of Class Serotonin-norepinephrine norepinephrine, such as concentration and reuptake inhibitor motivation, and in turn, improve social FDA approval July 26, 2013 date function. The FDA also has approved levomilnacipran for treating functional Manufacturer Forest Pharmaceuticals, Inc. impairment in depression.9 Dosage forms Extended–release capsules in 20 mg, 40 mg, 80 mg, and 120 mg strengths The norepinephrine uptake Adverse effects. Recommended 40 mg to 120 mg capsule inhibition of levomilnacipran might be dosage once daily with or without responsible for observed increases in heart food rate and blood pressure in some patients, and dose-dependent urinary hesitancy and erectile dysfunction in others. The drug has Clinical Point no significant effect on weight in depressed cards to use when speaking with irate or In theory, patients, compared with placebo. unhappy customers. At that point, her cervical The following case illustrates the benefits spine pain was barely noticeable and no longer levomilnacipran of levomilnacipran in a depressed patient interfered with function. should improve who suffers from chronic pain and impaired cognitive functions social function. linked to the action Vortioxetine of norepinephrine, CASE Mrs. C, age 44, was referred by her This agent has a novel multimodal mecha- outpatient psychologist and her primary nism of action (Table 3, page 34). It is an which, in turn, should care provider for management of refractory SSRI as well as a 5-HT1A full agonist and improve social depression. She did not respond to an SSRI, 5-HT3 receptor antagonist. Vortioxetine function an SNRI, or augmentation with bupropion and also has an inhibitory effect on 5-HT7 and aripiprazole. 5-HT1D receptors and partial agonism of Mrs. C was on disability leave from work 5-HT1B receptors. because of depression and cervical spine The downstream effect of this multi- pain that might have been related to repeti- modal action is an increase in dopamine, tive movement as a telephone customer norepinephrine, and acetylcholine activ- service representative. She complained of ity in the prefrontal cortex.10 These down- loss of motivation, fatigue, and high anxiety stream effects are thought to help restore about returning to work because of the many some cognitive deficits associated with unhappy customers she felt she had to soothe. depression.11 Levomilnacipran was started at 20 mg/d Vortioxetine is the only antidepressant for 2 days, then titrated to 40 mg/d for 5 days, among the 3 discussed in this article that 80 mg/d for 1 week, and 120 mg/d thereafter. was studied over a long period to ensure Her previous antidepressants, fluoxetine and that short-term benefits continue beyond bupropion, were discontinued while levomil- the 6- to 8-week acute Phase-III studies. A nacipran was titrated. high remission rate (61%) was observed in Mrs. C continued to receive weekly psy- patients who were treated on an open-label chotherapy and physical therapy and to take basis with vortioxetine, 10 mg/d, then ran- tizanidine, a muscle relaxant, and over-the- domized to maintenance with vortioxetine counter medications

Load more