DOCSLIB.ORG

Update on Psychiatric Medications

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Update on Psychiatric Medications An Update on Psychiatric Medications Mujeeb U Shad, M.D., M.S.C.S. Associate Professor of Psychiatry Oregon Heath & Science University, Portland Oregon Supervising Psychiatrist, Resident Outpatient Clinic at Samaritan Mental Health, OHSUCorvallis Oregon Staff Psychiatrist, Oregon State Hospital, Salem Oregon Aims & Objectives The audience will be presented with an update on recently and relatively recently approved psychopharmacological medications for major and minor psychiatric indications. It is NOT a review of efficacy or tolerability of psychotropic OHSUmedications New Psychotropics New Antidepressants Extended-Release trazodone (Oleptro) Desvenlafaxine (Pristiq) Duloxetine (Cymbalta) Vilazodone (Viibryd) Levomilnacipran (Fetzima) Vortioxetine (Trintellix) Esketamine – Intransal New antipsychotics Brexpiprazole (Rexulti) Cariprazine (Vraylar) OHSU Pimavanserin (Nuplazid) Sleep aids Suvorexant (Belsomra) Ramelteon (Rozerem) New Psychotropics Novel Indications: Medications to treat “adverse effects” such as Tardive Dyskinesia Valbenazine (Ingrezza) Deutetrabenazine (Austedo) New medication for Hypoactive Sexual Desire Disorder (HSSD) in females Flibanserin (Addyi) New medication to treat Pseudo-bulbar Affect OHSUDextromethorphan/Quinidine (Nuedexta) Vilazodone (Viibryd) 5HT1A OHSUSPARI SERT serotonin partial agonist / reuptake inhibitor Vilazodone: Pharmacokinetics OHSU Vilazodone: Dosing and Administration OHSU Vilazodone: Drug Interactions OHSU Levomilnacipran (Fetzima) • Latest SNRI approved for the treatment of major depression • Only SNRI with greater noradrenergic than serotonergic effects. • Dose start 20 mg QD x 2 days then increase to 40 mg QD • Half-Life: 12 hours OHSU• No effect of food on absorption Levomilnacipran (Fetzima) • Metabolized by CYP3A4 • Lower dose in patients with renal impairment • Nausea was most common adverse effect • Increased heart rate by 7.4 BPM • Increased BP 3.0 mm Hg in SBP and 3.2 mm Hg in OHSUDBP Levomilnacipran (Fetzima): Adverse Effects OHSU Venlafaxine (Effexor) Vs. Desvenlafaxine (Pristiq) CYP SERT SERT 2D6 venlafaxine desvenlafaxine OHSUNET NET Weight Gain with Desvenlafaxine in 5 RCT in MDD OHSU *P < .001 within-group change from baseline. †P < .001 desvenlafaxine versus placebo. ‡P < .01 versus desvenlafaxine 50 mg. §P ≤ .001 versus desvenlafaxine 50 mg. ‖P < .05 within-group change from baseline. **P < .001 versus desvenlafaxine 100 mg. ††P < .05 versus desvenlafaxine 200 mg. ‡‡P < .05 desvenlafaxine versus placebo. §§P < .01 desvenlafaxine versus placebo. Duloxetine SERT OHSUNET Comparison of SNRIs OHSU Trazodone XR (Oleptro) vs Placebo: Treatment for Major Depression • 412 pts randomized with 202 in the trazodone XR group and 204 in the placebo group. • 105/412 prematurely discontinued the study. • A two week titration to trazodone 150, 225, 300, or 375 mg/d vs. placebo followed by 42 d of post-titration dose. • Average post-titration dose = 310 mg for the trazodone XR group and 355 mg for the placebo group. • Significantly greater improvement in mean HAM-D 17 score in the trazodone OHSUXR group versus placebo by the first week of the double blind phase (day 7 of titration) maintained throughout the trial (P<.005, LOCF). Relative Binding Affinities of Trazodone • Relative selectivity for trazodone for four key binding sites: with the highest bars being the OHSUmost selective actions of trazodone. Trazodone affinities for receptors • Although 50 mg may fully saturate 5-HT2A and transporters. receptors, most of α1 receptors, about half of H1 receptors & 5HT pump, antidepressant effects require 5HT pump saturation (i.e., 300 Stahl SM. CNS Spectr. Vol 14, No 10. mg). 2009 Trazodone IR (Desyrel) vs Trazodone XR (Oleptra) Given Once Nightly • Trazodone IR given as 100 mg 3x/day for 9 days generates a saw tooth pattern of levels greatly sur- Trazodone XR at 300 mg a day addresses sedation as passing the minimum antidepressant concentration well as antidepressant effects. Trazodone IR used at the OHSUrequired all night long. usual sedating dosages can only be sedating. Peak • This results in adverse effects such as sedation levels of 100 mg IR are almost equal to 300 mg of XR. extending into next morning. By contrast, 300mg XR a day generates smoother peak and trough levels above minimum antidepressant concentration. Lower peaks levels from XR than IR are more tolerable. Stahl SM. CNS Spectr. Vol 14, No 10. 2009. Paradigm Shifts • The first effective antidepressant, imipramine was nonselective with multiple adverse effects. • This resulted in a quest for selectivity resulting in development of SSRIs and SNRIs. • However, despite being selective, SSRIs and SNRIs still have multiple adverse effects and unmet needs in the management of treatment-refractory depression. • This has made clinicians to use augmentation and/or combination strategies. • At the same time, a paradigm shift has occurred from selectivity to a multimodal approach to improve efficacy and tolerability. OHSU• Vortioxetine is one of the first antidepressants to represent a multimodal approach within a single molecule. Vortioxetine: Receptor Action Profile OHSU Vortioxetine Effect on Montgomery-Asberg Depression Rating Scale (MADRS) Score OHSU Vortioxetine Effect on Cognition OHSU Drug Interaction with Vortioxetine • Vortioxetine is metabolized by CYP2D6 and 3A4. • Thus, inhibitors of CYP2D6 will inhibit metabolism • Inducers of CYP3A4 will increase the metabolism OHSUof vortioxetine. Ketamine OHSU KETAMINE Synthesized in 1962, first used in humans in 1965, released for clinical use in 1970 Antagonist to NMDA Receptor. Racemic mixture of S and R ketamine. S isomer is 3 x more potent and has fewer psychotomimetic effects. OHSU Only 20% bioavailability after oral use. OHSU OHSU FDA Approves Fast-Acting Esketamine for Treatment-Resistant Depression • Esketamine (Spravato) nasal spray to be used in conjunction with an oral antidepressant for treatment- resistant depression. • Esketamine is the first medication for depression with a new mechanism of action since fluoxetine was approved in 1988. • Because of risks dissociation and misuse, esketamine is subject to a comprehensive Risk Evaluation and Mitigation Strategy (REMS) program and carries a black-box warning. • Patients can take esketamine only under supervision by a certified physician and must be monitored for at least two hours post-administration. • In preclinical trials, 223 patients with treatment-resistant depression were randomized to receive twice weekly doses of intranasal esketamine or placebo. • Those on active nasal spray experienced greater improvement in their depression symptoms at 4-weeks OHSUcompared to placebo nasal spray. • In a longer study, patients who continued taking esketamine were 51% less likely to relapse than those on placebo. • Two other short-term trials did not meet prespecified statistical tests for demonstrating effectiveness. Why Esketamine? • Esketamine is 3-4 times more potent than arketamine • Thus, lower dose OHSUvolume OHSU OHSU Change in MADRS Score from baseline OHSU OHSU Change in MADRS Score from baseline OHSU Changes in Mean MADRS Score in the Open Label Phase OHSU During open-label period esketamine was continued to be given twice/wk. followed by once/wk. followed by once every month. Clinician-Administered Dissociative States Scale (CADSS) (Panel A) OHSU Most Frequently Reported Adverse Effects OHSU Canuso et al. AJP 2018 Conclusions • Intranasal 28, 56, and 84 mg, but not 14 mg, were significantly better than placebo in reducing depressive symptoms as demonstrated by the changes in MADRS total score. • The antidepressant effects of esketamine persist for at least 8-weeks after the last dose in the open label follow up period • Esketamine can produce number of transient adverse effects, such as nausea, dizziness, dysgeusia, and dissociation. • Of note, dissociative symptoms were limited to the immediate post- OHSUadministration period and attenuated after repeated dosages over time. Brexpiprazole (Rexulti) OHSU D2 D3 5HT7 D4 H1 5HT6 5HT 5HT 5HT 1 5HT 5HT D1 1A 2A 2B 2C 1B Cariprazine • Schizophrenia dose range = starting with 1.5 mg and then increasing to 6 mg once daily • Can be increased to 3 mg on Day 2 • Manic or Mixed Episodes dose range is 3 to 6 mg once daily • CYP3A4 is responsible for the formation and elimination of active metabolites of cariprazine. OHSU• Dose adjustments required For 5HT 5HT CYP3A4 inhibitors and inducers 2B 1A H1 5HT 2C D3 D2 5HT 5HT7 1 2A OHSUNovel Indications for Psychotropics Flibanserin (ADDYI) • Indication: hypoactive sexual desire disorder (HSDD) in premenopausal women • Approval Date: August 18, 2015 • MOA: Serotonin (5-HT) receptor 1A agonist and 5-HT2A • Dose: 100 mg PO once daily at bedtime • Discontinue treatment after 8 weeks if no OHSUimprovement Product Information: ADDYI (flibanserin) oral tablets. Sprout Pharmaceuticals, Inc. Raleigh, NC, 2015. Flibanserin (ADDYI) • Black Box Warning: Contraindicated with alcohol, moderate- strong CYP3A4 inhibitors, or hepatic impairment due to increased risk of severe hypotension and syncope (only available though ADDYI REMS program) • Adverse Effects: Dizziness, somnolence, nausea, fatigue, insomnia, dry mouth • Approval based on BEGONIA trial, which resulted in significant improvements in the number of satisfying sexual events and sexual OHSUdesire versus placebo Product Information: ADDYI (flibanserin) oral tablets. Sprout Pharmaceuticals, Inc. Raleigh, NC, 2015. Flibanserin (ADDYI) • Place in Therapy: first FDA-approved
Load more

Recommended publications
  • Dextromethorphan Attenuates Sensorineural Hearing Loss in an Animal Model and Population-Based Cohort Study
    International Journal of Environmental Research and Public Health Article Dextromethorphan Attenuates Sensorineural Hearing Loss in an Animal Model and Population-Based Cohort Study Hsin-Chien Chen 1,* , Chih-Hung Wang 1,2 , Wu-Chien Chien 3,4 , Chi-Hsiang Chung 3,4, Cheng-Ping Shih 1, Yi-Chun Lin 1,2, I-Hsun Li 5,6, Yuan-Yung Lin 1,2 and Chao-Yin Kuo 1 1 Department of Otolaryngology-Head and Neck Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan; [email protected] (C.-H.W.); [email protected] (C.-P.S.); [email protected] (Y.-C.L.); [email protected] (Y.-Y.L.); [email protected] (C.-Y.K.) 2 Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, Taiwan 3 School of Public Health, National Defense Medical Center, Taipei 114, Taiwan; [email protected] (W.-C.C.); [email protected] (C.-H.C.) 4 Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan 5 Department of Pharmacy Practice, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan; [email protected] 6 School of Pharmacy, National Defense Medical Center, Taipei 114, Taiwan * Correspondence: [email protected]; Tel.: +886-2-8792-7192; Fax: +886-2-8792-7193 Received: 31 July 2020; Accepted: 28 August 2020; Published: 31 August 2020 Abstract: The effect of dextromethorphan (DXM) use in sensorineural hearing loss (SNHL) has not been fully examined. We conducted an animal model and nationwide retrospective matched-cohort study to explore the association between DXM use and SNHL.
    [Show full text]
  • Vortioxetine (Trintellix) Or Vilazodone (Viibryd)
    Clinical Policy: Polyserotonergic Antidepressants- Vortioxetine (Trintellix) or Vilazodone (Viibryd) Reference Number: AZ.CP.PMN.20 Effective Date: 06.17 Last Review Date: 07.20 Line of Business: Arizona Medicaid Revision Log See Important Reminder at the end of this policy for important regulatory and legal information. Description Vortioxetine (Trintellix®) and Vilazodone (Viibryd®) are antidepressants that enhance serotoninergic activity via multiple mechanisms FDA approved indications Trintellix and Viibryd are indicated for the treatment of major depressive disorder. Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria. It is the policy of Arizona Complete Health Trintellix and Viibryd are medically necessary when the following criteria are met: I. Initial Approval Criteria A. Depression (must meet all): 1. Diagnosis of major depressive disorder (MDD); 2. For Trintellix- age ≥ 18 years and for Viibryd- age ≥ 12 years; 3. Failure of a ≥ 8 week trial of one SSRI at up to maximally indicated doses unless contraindicated or clinically significant adverse effects are experienced; 4. Failure of a ≥ 8 week trial of one SNRI at up to maximally indicated doses unless contraindicated or clinically significant adverse effects are experienced; 5. Failure of one SSRI or SNRI used adjunctively with one of the following: bupropion, mirtazapine, or tricyclic antidepressant (TCA) unless contraindicated 6. Dose of Trintellix does not exceed 20 mg/day (1 tablet/day) or dose of Viibryd does not exceed 40 mg/day (1 tablet/day). Approval duration: 12 months B. Other diagnoses/indications 1. Refer to the off-label use policy for the relevant line of business if diagnosis is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized): AZ.CP.PMN.53 for Arizona Medicaid.
    [Show full text]
  • Withdrawal Symptoms Following Discontinuation of Vortioxetine—Retrospective Chart Review
    pharmaceuticals Article Withdrawal Symptoms Following Discontinuation of Vortioxetine—Retrospective Chart Review Marcin Siwek 1,*, Adrian Andrzej Chrobak 2 , Aleksandra Gorostowicz 3, Anna Julia Krupa 3 and Dominika Dudek 2 1 Department of Affective Disorders, Jagiellonian University Medical College, Kopernika Street 21a, 31-501 Kraków, Poland 2 Department of Adult Psychiatry, Jagiellonian University Medical College, Kopernika Street 21a, 31-501 Kraków, Poland; [email protected] (A.A.C.); [email protected] (D.D.) 3 Department of Psychiatry, Jagiellonian University Medical College, Kopernika Street 21a, 31-501 Kraków, Poland; [email protected] (A.G.); [email protected] (A.J.K.) * Correspondence: [email protected]; Tel.: +48-12-424-87-00 Abstract: The efficacy of vortioxetine has been proven in many studies, but data concerning dis- continuation symptoms (DS) after vortioxetine withdrawal is scarce. The aim of our study is to systematically evaluate the prevalence, determinants, and clinical features of vortioxetine DS in a retrospective chart review. Data were obtained from medical records of 263 adult patients with depressive disorders who discontinued former vortioxetine treatment. DS were observed in eight (3%) patients after 71–375 days (median 272) of treatment. DS emerged after median three days following vortioxetine withdrawal and lasted for median seven days. The clinical presentation of DS involved: emotional lability (100% of patients), irritability (75%), sudden worsening of mood (75%), nervousness (37.5%), and agitation (37.5%). Median DESS score was four (range of four to six). DS Citation: Siwek, M.; Chrobak, A.A.; were significantly more prevalent after accidental vs.
    [Show full text]
  • Print Your Symptom Diary
    MEDICATION GUIDE FETZIMA® (fet-ZEE-muh) (levomilnacipran) extended-release capsules, for oral use What is the most important information I should know about FETZIMA? FETZIMA may cause serious side effects, including: • Increased risk of suicidal thoughts or actions in some children, adolescents, and young adults. FETZIMA and other antidepressant medicines may increase suicidal thoughts or actions in some children and young adults, especially within the first few months of treatment or when the dose is changed. FETZIMA is not for use in children. o Depression or other serious mental illnesses are the most important causes of suicidal thoughts or actions. Some people may have a higher risk of having suicidal thoughts or actions. These include people who have (or have a family history of) depression, bipolar illness (also called manic-depressive illness) or have a history of suicidal thoughts or actions. How can I watch for and try to prevent suicidal thoughts and actions? o Pay close attention to any changes, especially sudden changes in mood, behavior, thoughts, or feelings, or if you develop suicidal thoughts or actions. This is very important when an antidepressant medicine is started or when the dose is changed. o Call your healthcare provider right away to report new or sudden changes in mood, behavior, thoughts, or feelings. o Keep all follow-up visits with your healthcare provider as scheduled. Call your healthcare provider between visits as needed, especially if you have concerns about symptoms. Call your healthcare provider or
    [Show full text]
  • Serotonin 2A Activation and a Novel Therapeutic Drug
    Psychopharmacology (2018) 235:3083–3091 https://doi.org/10.1007/s00213-018-5042-1 THEORETICAL AND METHODOLOGICAL PERSPECTIVE The neuropharmacology of sleep paralysis hallucinations: serotonin 2A activation and a novel therapeutic drug Baland Jalal1 Received: 23 April 2018 /Accepted: 17 September 2018 /Published online: 5 October 2018 # The Author(s) 2018 Abstract Sleep paralysis is a state of involuntary immobility occurring at sleep onset or offset, often accompanied by uncanny Bghost-like^ hallucinations and extreme fear reactions. I provide here a neuropharmacological account for these hallucinatory experiences by evoking the role of the serotonin 2A receptor (5-HT2AR). Research has shown that 5-HT2AR activation can induce visual hallucinations, Bmystical^ subjective states, and out-of-body experiences (OBEs), and modulate fear circuits. Hallucinatory experiences triggered by serotonin—serotonergic (Bpseudo^) hallucinations, induced by hallucinogenic drugs—tend to be Bdream-like^ with the experiencer having insight (Bmeta-awareness^) that he is hallucinating, unlike dopaminergic (Bpsychotic^ and Blife-like^) hallucinations where such insight is lost. Indeed, hallucinatory experiences during sleep paralysis have the classic features of serotonergic hallucinations, and are strikingly similar to perceptual and subjective states induced by hallucinogenic drugs (e.g., lysergic acid diethylamide [LSD] and psilocybin), i.e., they entail visual hallucinations, mystical experiences, OBEs, and extreme fear reactions. I propose a possible mechanism whereby serotonin could be functionally implicated in generating sleep paralysis hallucinations and fear reactions through 5-HT2AR activity. Moreover, I speculate on the role of 5-HT2C receptors vis-à-vis anxiety and panic during sleep paralysis, and the orbitofrontal cortex—rich with 5-HT2A receptors—in influencing visual pathways during sleep paralysis, and, in effect, hallucinations.
    [Show full text]
  • Levomilnacipran (Fetzima®) Indication
    Levomilnacipran (Fetzima®) Indication: Indicated for the treatment of major depressive disorder (MDD), FDA approved July 2013. Mechanism of action Levomilnacipran, the more active enantiomer of racemic milnacipran, is a selective SNRI with greater potency for inhibition of norepinephrine relative to serotonin reuptake Compared with duloxetine or venlafaxine, levomilnacipran has over 10-fold higher selectivity for norepinephrine relative to serotonin reuptake inhibition The exact mechanism of the antidepressant action of levomilnacipran is unknown Dosage and administration Initial: 20 mg once daily for 2 days and then increased to 40 mg once daily. The dosage can be increased by increments of 40 mg at intervals of two or more days Maintenance: 40-120 mg once daily with or without food. Fetzima should be swallowed whole (capsule should not be opened or crushed) Levomilnacipran and its metabolites are eliminated primarily by renal excretion o Renal impairment Dosing: Clcr 30-59 mL/minute: 80 mg once daily Clcr 15-29 mL/minute: 40 mg once daily End-stage renal disease (ESRD): Not recommended Discontinuing treatment: Gradually taper dose, if intolerable withdrawal symptoms occur, consider resuming the previous dose and/or decrease dose at a more gradual rate How supplied: Capsule ER 24 Hour Fetzima Titration: 20 & 40 mg (28 ea) Fetzima: 20 mg, 40 mg, 80 mg, 120 mg Warnings and Precautions Elevated Blood Pressure and Heart Rate: measure heart rate and blood pressure prior to initiating treatment and periodically throughout treatment Narrow-angle glaucoma: may cause mydriasis. Use caution in patients with controlled narrow- angle glaucoma Urinary hesitancy or retention: advise patient to report symptoms of urinary difficulty Discontinuation Syndrome Seizure disorders: Use caution with a previous seizure disorder (not systematically evaluated) Risk of Serotonin syndrome when taken alone or co-administered with other serotonergic agents (including triptans, tricyclics, fentanyl, lithium, tramadol, tryptophan, buspirone, and St.
    [Show full text]
  • Atypical Antipsychotics TCO 02.2018
    Therapeutic Class Overview Atypical Antipsychotics INTRODUCTION • Antipsychotic medications have been used for over 50 years to treat schizophrenia and a variety of other psychiatric disorders (Miyamato et al 2005). • Antipsychotic medications generally exert their effect in part by blocking dopamine (D)-2 receptors (Jibson et al 2017). • Antipsychotics are divided into 2 distinct classes based on their affinity for D2 and other neuroreceptors: typical antipsychotics, also called first-generation antipsychotics (FGAs), and atypical antipsychotics, also called second- generation antipsychotics (SGAs) (Miyamato et al 2005). • Atypical antipsychotics do not have a uniform pharmacology or mechanism of action; these differences likely account for the different safety and tolerability profiles of these agents (Clinical Pharmacology 2020, Jibson et al 2017). The atypical antipsychotics differ from the early antipsychotics in that they have affinity for the serotonin 5-HT2 receptor in addition to D2. Clozapine is an antagonist at all dopamine receptors (D1-5), with lower affinity for D1 and D2 receptors and high affinity for D4 receptors. Aripiprazole and brexpiprazole act as partial agonists at the D2 receptor, functioning as an ○ agonist when synaptic dopamine levels are low and as an antagonist when they are high. Cariprazine is a partial agonist at D2 and D3. Pimavanserin does not have dopamine blocking activity and is primarily an inverse agonist at 5-HT2A receptors. The remaining atypical antipsychotics share the similarity of D2 and 5-HT2A
    [Show full text]
  • M2021: Pharmacogenetic Testing
    Pharmacogenetic Testing Policy Number: AHS – M2021 – Pharmacogenetic Prior Policy Name and Number, as applicable: Testing • M2021 – Cytochrome P450 Initial Presentation Date: 06/16/2021 Revision Date: N/A I. Policy Description Pharmacogenetics is defined as the study of variability in drug response due to heredity (Nebert, 1999). Cytochrome (CYP) P450 enzymes are a class of enzymes essential in the synthesis and breakdown metabolism of various molecules and chemicals. Found primarily in the liver, these enzymes are also essential for the metabolism of many medications. CYP P450 are essential to produce many biochemical building blocks, such as cholesterol, fatty acids, and bile acids. Additional cytochrome P450 are involved in the metabolism of drugs, carcinogens, and internal substances, such as toxins formed within cells. Mutations in CYP P450 genes can result in the inability to properly metabolize medications and other substances, leading to increased levels of toxic substances in the body. Approximately 58 CYP genes are in humans (Bains, 2013; Tantisira & Weiss, 2019). Thiopurine methyltransferase (TPMT) is an enzyme that methylates azathioprine, mercaptopurine and thioguanine into active thioguanine nucleotide metabolites. Azathioprine and mercaptopurine are used for treatment of nonmalignant immunologic disorders; mercaptopurine is used for treatment of lymphoid malignancies; and thioguanine is used for treatment of myeloid leukemias (Relling et al., 2011). Dihydropyrimidine dehydrogenase (DPD), encoded by the gene DPYD, is a rate-limiting enzyme responsible for fluoropyrimidine catabolism. The fluoropyrimidines (5-fluorouracil and capecitabine) are drugs used in the treatment of solid tumors, such as colorectal, breast, and aerodigestive tract tumors (Amstutz et al., 2018). A variety of cell surface proteins, such as antigen-presenting molecules and other proteins, are encoded by the human leukocyte antigen genes (HLAs).
    [Show full text]
  • SPRAVATO® Esketamine Hydrochloride DATA SHEET
    SPRAVATO® esketamine hydrochloride DATA SHEET 1. PRODUCT NAME SPRAVATO® esketamine hydrochloride 32.3mg (equivalent to 28mg esketamine) nasal spray 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each single use nasal spray device delivers two sprays, one spray into each nostril. Total volume of drug product per device to be delivered is 0.2 mL containing a total of 32.3 mg of esketamine hydrochloride (equivalent to 28 mg of esketamine). For the full list of excipients, see Section 6.1 List of Excipients. 3. PHARMACEUTICAL FORM Nasal spray, solution. Clear, colourless, aqueous solution. 4. CLINICAL PARTICULARS 4.1 Therapeutic Indications SPRAVATO in conjunction with an oral antidepressant, is indicated for: - treatment resistant depression (Major Depressive Disorder in adults who have not responded adequately to at least two different antidepressants of adequate dose and duration to treat the current depressive episode). - rapid reduction of depressive symptoms in patients with Major Depressive Disorder who have acute suicidal ideation or behaviour. SPRAVATO is not indicated to prevent suicide or in reducing suicidal ideation or behaviour (see section 4.4. Special Warnings And Precautions For Use) 4.2 Dose and method of administration In patients with TRD, SPRAVATO should be administered in conjunction with a newly initiated oral antidepressant (AD) therapy. In patients with MDSI, SPRAVATO should be administered in conjunction with standard of care therapy. During the Phase III MDSI clinical program, standard of care oral AD treatment (either AD monotherapy or AD plus augmentation therapy) was initiated or optimised. Important Considerations Prior to Initiating and During Therapy SPRAVATO must be administered under the direct supervision of a healthcare provider.
    [Show full text]
  • CDPHP Medicare Advantage 2021 Part D Prior Authorization Criteria
    CDPHP Medicare Advantage 2021 Part D Prior Authorization Criteria The following guidelines outline the Part D drugs that require prior authorization through the CDPHP pharmacy department. Please be aware that these guidelines do not reflect those instances in which it is the member’s responsibility to seek prior authorization. Coverage for a service is subject to the member’s eligibility, specific contract benefits, and CDPHP policy. Requests for a service that does not meet criteria outlined in the CDPHP Medicare Advantage pharmacy policies or for an extension beyond what has been approved by CDPHP should be directed to the pharmacy department at (518) 641-3784. POLICIES Policy Reference/Type of Service Requiring Prior Authorization Effective Date: September 1, 2021 abiraterone (ZYTIGA) Covered indications: All Medically-Accepted Indications (FDA approved and 1350/20.000278 compendia-supported). Exclusions: None PA applies to new starts only Approvals: 12 months. ACNE 1350/20.000118 Covered indications: All Medically-Accepted Indications (FDA approved and • avita cream/gel compendia-supported). • tretinoin cream/gel Criteria: Enrollee has tried or prescriber has considered using one of the accepted therapies noted in national guidelines, including, but not limited to topical benzoyl peroxide, topical antibiotics, systemic antibiotics but deemed one or all of them inappropriate for the enrollee. Exclusions: Cosmetic Use. Approvals: 12 months. ACTIMMUNE (Interferon-Gamma 1B) Covered indications: All Medically-Accepted Indications (FDA approved and 1350/20.000278 compendia-supported). Exclusions: None PA applies to new starts only Approvals: 12 months. ADEMPAS (riociguat) Covered indications: All FDA-approved indications not otherwise excluded 1350/20.000278 from Part D.
    [Show full text]
  • Around the Corner Canadian Equity Research Emerging Companies and Industries to Watch 3 March 2020
    Around the Corner Canadian Equity Research Emerging companies and industries to watch 3 March 2020 Tania Gonsalves, CFA | Analyst | Canaccord Genuity Corp. (Canada) | [email protected] | 1.416.996.8346 Scott McFarland | Associate | Canaccord Genuity Corp. (Canada) | [email protected] | 1.416.998.7202 Around the Corner highlights what we believe are some of the most exciting Psychedelic-derived medicines and therapies emergent private companies in Canada, and/or industry themes and trends which are yet to be fully represented in the Mental health miracle or another bad trip? public markets. When most of us think of psychedelic drugs, we think of the 1960s counterculture. We We aim to offer insight into early industry think of anti-establishment, anti-war, anti-capitalist hippies, Woodstock, tie-dye, Lucy in trends, educate investors about private the Sky, peace, love and bell bottom jeans. But before psychedelics became ingrained in companies that are making a mark, and the counterculture, they were found in a lab. The first wave of scientific research on identify companies that may enter the psychedelics took place between 1950-65. Sandoz Pharmaceutics, what is now Novartis public markets in the future. AG (NVS-NYSE), the third largest pharmaceutical company in the world, used to market We do not provide any ratings or price LSD and psilocybin for psychotherapeutic purposes. Psychedelics weren’t born of the targets, nor should any be inferred, for counterculture. They were killed by it. The proliferation of recreational use spurred any uncovered company featured in government intervention and by 1971, psilocybin, LSD, ibogaine, mescaline, peyote, Around the Corner.
    [Show full text]
  • Levomilnacipran for the Treatment of Major Depressive Disorder
    Out of the Pipeline Levomilnacipran for the treatment of major depressive disorder Matthew Macaluso, DO, Hala Kazanchi, MD, and Vikram Malhotra, MD An SNRI with n July 2013, the FDA approved levomil- Table 1 once-daily dosing, nacipran for the treatment of major de- Levomilnacipran: Fast facts levomilnacipran pressive disorder (MDD) in adults.1 It is I Brand name: Fetzima decreased core available in a once-daily, extended-release formulation (Table 1).1 The drug is the fifth Class: Serotonin-norepinephrine reuptake symptoms of inhibitor serotonin-norepinephrine reuptake inhibi- MDD and was well Indication: Treatment of major depressive tor (SNRI) to be sold in the United States disorder in adults tolerated in clinical and the fourth to receive FDA approval for FDA approval date: July 26, 2013 trials treating MDD. Availability date: Fourth quarter of 2013 Levomilnacipran is believed to be the Manufacturer: Forest Pharmaceuticals more active enantiomer of milnacipran, Dosage forms: Extended–release capsules in which has been available in Europe for 20 mg, 40 mg, 80 mg, and 120 mg strengths years and was approved by the FDA in Recommended dosage: 40 mg to 120 mg 2009 for treating fibromyalgia. Efficacy of capsule once daily with or without food levomilnacipran for treating patients with Source: Reference 1 MDD was established in three 8-week ran- domized controlled trials (RCTs).1 cial and occupational functioning in addi- Clinical implications tion to improvement in the core symptoms Levomilnacipran is indicated for treating of depression.5
    [Show full text]