What s New in Depression in 2016? By: Phyliss Nicole Taylor, MD UF Health Jacksonville Psychiatry

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1 What s New in Depression in 2016? By: Phyliss Nicole Taylor, MD UF Health Jacksonville Psychiatry

2 New Depression Screening Guidelines US Preventive Services Task Force (USPSTF) updated its 2009 recommendations [1] General adult population aged 18 years and older, including older adults Adding screening of pregnant and postpartum women (grade B= moderate level benefit) Screening should be implemented with adequate systems in place to ensure accurate diagnosis, effective treatment, and appropriate follow-up PCP s to provide the screening for all patients, using effective screening tests such as the Patient Health Questionnaire, the Hospital Anxiety and Depression Scales in adults, the Geriatric Depression Scale in older adults, and the Edinburgh Postnatal Depression Scale in postpartum and pregnant women

3 Antidepressants in Pregnancy and Autism Use of SSRI s during the 2 nd or 3 rd trimester increases the risk of ASD in children, even after considering maternal depression [2] No increased risk for ASD was observed with the use of antidepressants during the first trimester 87% increase risk of having a child with autistic spectrum disorder, but absolute risk low The combined use of drugs from two or more antidepressant drug classes was associated with the highest risk of having a child with ASD Must weigh risks of exposure to SSRI vs. exposure to untreated depression for child

4 Rexulti (Brexpiprazole) Manufacturer: Otsuka FDA Approval Date: July 2015 Indications: For the adjunctive treatment of major depression and schizophrenia Recommended dosing (for depression): Start 0.5mg or 1 mg daily and titrate weekly to target dose of 2 mg daily; max =3 mg daily Most common side effects : akathisia (7-14%) and weight gain (<8%) MOA: atypical antipsychotic with combination of partial agonist activity at serotonin 5-HT1A and dopamine D2 receptors, and antagonist activity at serotonin 5-HT2A receptors

5 Brintellix (Vortioxetine) Manufacturer: Takeda Pharmaceuticals USA FDA Approval Date: October 2013 Indications: For the treatment of Major Depressive Disorder; Improved cognitive function in major depression Recommended dosing: Start with 10 mg daily and can titrate up to 20 mg daily Most Common Side effects: nausea (21-32%), constipation, vomiting MOA: serotonin modulator and stimulator; inhibition of the reuptake of serotonin (5-HT); 5-HT3 receptor antagonism and 5-HT1A receptor agonism

6 Fetzima (Levomilnacipran) Manufacturer: Forest Laboratories FDA Approval Date: July 2013 Indication: For the treatment of major depressive disorder Recommended dosing: Start 20 mg daily x 2 days, then increase to 40 mg daily; titrate by 40 mg dose every 2 days until max= 120 mg daily MOA: extended release selective norepinephrine and serotonin reuptake inhibitor Enantiomer of Milnacipran (Savella)which is indicated for treatment of fibromyalgia

7 Role of Folate and Depression Borderline low or deficient serum or red blood cell folate levels have been detected in 15% to 38% of adults diagnosed with depressive disorders. [3] Low folate levels have been linked to poorer SSRI response Folate supplementation to antidepressants may lead to faster and more robust response and decreased relapses. Several brands of prescription folate on market: Enlyte, Deplin, Cerefolin

8 Ketamine and Depression Anesthetic or analgesic; illicitly used as hallucinogen MOA: Blocking the activity of glutamate on the N-methyl-D-aspartate (NMDA) receptor; also acts on opioid receptors and monoamine transporters Common side effects: psychological reactions as the medication wears off, elevated blood pressure and muscle tremors Rapid antidepressant effect in patients with treatment resistant unipolar and bipolar depression and people in suicidal crisis in ER[4] Given by a single IV infusion at doses less than those used in anesthesia, but may require multiple doses over a few days; intranasal spray also being studied Rapid response (within 1-2 hours) and relatively sustained (about 1 2 weeks long) reduction - in symptoms in some people

9 Opioids for Depression The short-term use of ultra-low-dose ( mg/day) sublingual buprenorphine for acute (<4 weeks), symptomatic, safe treatment for suicidal ideation [5] Useful adjunctive treatment to antidepressants, worked well in Borderline PD Most common side effects: fatigue, nausea, dry mouth, and constipation No withdrawal symptoms noted with abrupt discontinuation Caution in substance abusers MOA: Partial mu agonist and a potent kappa antagonist

10 Buprenorphine/Samidorphan (ALKS 5461) Phase III Clinical Trials for FDA approval for treatment resistant major depression in adjunct to SSRI or SNRI antidepressant [6] Manufacturer: Alkermes, Inc. Dosing: single SL tablet taken once daily MOA: Buprenorphine: partial mu agonist and a potent kappa antagonist; Samidorphan: a potent mu-opioid receptor antagonist (block the abuse and addiction of buprenorphine) Most common side effects: nausea, vomiting, and dizziness No indications of opioid withdrawal and no consistent signals of abuse liability associated with the treatment

11 Pharmacogenomic Testing Analyzes how patients genes may affect metabolism and response to certain antidepressants (and other medications) Genetic variations at CYP2D6 and CYP2C19 may affect serum levels of medications and predict more drug-drug interactions in people with comorbid medical conditions Polymorphisms in SLC6A4 (promoter region of the serotonin transporter gene) and 5-HT polymorphisms in serotonin receptors (2A and 2C subtypes) appear to influence SSRI response and side effects MTHFR tests provide information about folate deficiency which can affect depression and response to antidepressants Based on patients genetic status, physicians could predict their response to certain drugs, leading to better efficacy, fewer adverse drug reactions, and a better cost-benefit ratio FDA includes pharmacogenomics information in their labels DNA collected by buccal swab in office and sent for analysis, results to physician in 2-3 days Reimbursed by most insurances and Patient Assistance Plan is available.

12 Works Cited 1. Siu, Albert. Screening for Depression in Adults: US Preventive Services Task Force Recommendation Statement. Journal of American Medical Association (2016): Print. 2. Boukhris, Takoua et al. Antidepressant Use During Pregnancy and the Risk of Autism Spectrum Disorder in Children. Journal of American Medical Association Pediatrics (2016): Print. 3. Alpert, Jonathan et al. Nutrition and Depression: The Role of Folate. Medscape Psychiatry & Mental Health E Journal 2.1 (1997). Medscape. Web. 12 March Caddy C et al. Ketamine and other glutamate receptor modulators for depression in adults. Cochrane Database Systematic Reviews. (2015). Medscape. Web 12 March Yovell, Yoram et al. Ultra Low-Dose Buprenorphine as a Time-Limited Treatment for Severe Suicidal Ideation: A Randomized Controlled Trial. American Journal of Psychiatry (2015). Psychiatry Online. Web. 12 March Fava, Maurizio et al. Opioid Modulation With Buprenorphine/Samidorphan as Adjunctive Treatment for Inadequate Response to Antidepressants: A Randomized Double Blind Placebo Controlled Trial. American Journal of Psychiatry (2015). Psychiatry Online. Web. 12 March 2016