KPhA s 133 rd Annual Meeting and Trade Show

Transcription

1 KPhA s 133 rd Annual Meeting and Trade Show

2 KPhA s 133 rd Annual Meeting and Trade Show Be the Critical Link DoubleTree by Hilton Hotel Overland Park, Kansas End of the Line: Shocking therapies for treatment-resistant depression Saturday, September 21, 2013 Niccole Winistoerfer, PharmD, BCPS, BCPP

3 3 Disclosures The speaker has no conflicts of interest or disclosures Any mention of non-fda approved treatments/procedures will denoted by an *

4 4 Program Summary This program will aim to review the potential options for treatment-resistant depression, including pharmacological and non-pharmacological options. Emphasis will be placed on the impact of the pharmacist in helping patients make the most of their therapy while ensuring adverse events are minimized. A discussion of old and new therapies with specific examples of the benefits of the pharmacist will be discussed. At the end of the presentation, the pharmacist should be able to identify areas in which (s)he can make appropriate recommendations based on the type of therapy suggested, as well as serving as a resource of information for patients.

5 5 Learning Objectives 1. Describe treatment-resistant depression (TRD) and its implications for patient care 2. Explore emerging alternative therapies for TRD 3. Understand the role of electroconvulsive therapy (ECT) in treatment, as well as its potential impact on medication selection 4. Examine the various types of focal brain stimulation in regards to treatment of depression 5. Identify the potential use of ketamine in TRD, as well as implications for the use of this medication

6 6 Epidemiology of Depression ( 1,2,3,4) Lifetime prevalence in the US is~17% 4 to 10% of Americans affected annually STAR*D showed ~1/3 response rate to the first antidepressant (AD), with <30% response rate to a second ~43% of patient in STAR*D sustained recovery Significant source of morbidity, mortality, and decreased quality of life

7 7 Treatment-resistant depression (TRD) No universal definition (2) Failure to achieve remission after two or more AD trials of adequate dose and duration Failure to achieve remission with one AD increases risk of relapse/ recurrence (1) STAR*D suggests ~30% will not achieve remission after four adequate AD trials (4)

8 8 Impact on Society (1) A leading cause of morbidity, mortality and disability Increased risk of suicide Higher health care utilization Significant increases in healthcare costs ~$8622 per TRD patient; ~$4547 non-trd patient

9 9 Debbie Debbie is a 34 yr. old female being treated for depression. Debbie reports an increase in intrusive thoughts, including suicidal ideation, even though she s been compliant with her medications. She also reports low energy, apathy, and a lack of motivation. She recently told her family that she thought they would be better off without her. PMH: Migraines Hypertension Current medications: Fluoxetine 60mg daily Hydrochlorothiazide 25mg daily Sumatriptan mg as needed for migraine

10 10 Current treatment strategies (2,5) Switch antidepressants Within classes Between classes Add an adjunctive medication Second-generation antipsychotic Mood stabilizer Additional antidepressant with unique MOA Use of medical food supplements Folate Fish oil Non-pharmacological options

11 11 FDA approved medications (2,5,7) Fluoxetine Fluvoxamine Sertraline Citalopram Escitalopram Paroxetine Duloxetine Venlafaxine Desvenlafaxine Levomilnacipran Bupropion MAO - I Mirtazapine TCAs Vilazodone Aripiprazole Quetiapine Olanzapine D-methylfolate

12 12 What next? Electroconvulsive therapy Focal brain stimulation Novel medication therapies

13 13 Electroconvulsive therapy (ECT) (6) First ECT performed in 1938 Schizophrenia Decreased utilization during the 60s and 70s Media Ethical issues Recent resurgence in use 40 to 60% response rate with TRD More rapid onset than medications

14 14 ECT (6) Controlled seizure 30 to 90 seconds Mechanism of action Monoamine neurotransmitter theory Neuroendocrine theory Anticonvulsant theory Neurotrophic theory Informed consent Thorough explanation of procedure

15 15 Selection criteria (6) Medication failure and/or partial response to medications Usually a minimum of three trials of at least two different medication classes of an adequate duration Severity of illness, urgent improvement needed FDA cleared indications Depression Catatonia Schizophrenia, schizophreniform, schizoaffective Bipolar disorder

16 16 Adverse effects (6) Cognitive effects Transient confusion Anterograde amnesia Retrograde amnesia Physical effects Headache Nausea/vomiting Generalized muscle aches Jaw pain

17 17 Pre-ECT checklist (6) Family support Medical clearance May require a cardiac workup CT scan and/or MRI Neurology input (if necessary) History of seizure disorder Traumatic brain injury Transportation MEDICATION REVIEW

18 18 Medication review All medications including herbals, over-the-counter medications, and supplements Seizure threshold alterations Any medication that could have an adverse effect if held and/or given prior to the procedure Drug interactions medications administered during the procedure Allergy check

19 19 Medication review Absolute holds: Theophylline Reserpine MAOIs Benzodiazepines Probable holds: Lithium Anticonvulsants Caveats: Sleeping aids Antihypertensives

20 20 Now for the shock. (6) Acute ECT Three times a week for approximately four weeks Maintenance ECT Patient-specific Conscious sedation Performed in the PACU/OR area NPO after midnight Less than 10 minutes from start to finish A few hours for the entire process

21 21 Post-ECT expectations (6) Post-ictal state Tiredness Confusion and/or grogginess Restrictions No driving for at least 48 hours after treatment Supervision for at least 12 hours after treatment Adjunctive medications Caffeine Non-steroidal anti-inflammatories Ketoralac Ibuprofen

22 22 So now what? Is Debbie out of options? Not quite yet.

23 23 Focal brain stimulation Transcranial magnetic stimulation (TMS) Vagus nerve stimulation (VNS) Transcranial DC stimulation (tdcs) Direct cortical stimulation (DCS) Deep brain stimulation (DBS)

24 24 Vagus nerve stimulation (VNS) (2,8) FDA approved for TRD in 7/2005 Programmable device Battery-powered generator attached to a wire that coils around the Vagus nerve Mechanism of action Unclear, probably multifactorial Adverse effects Hoarseness, voice alterations Cough, dyspnea Neck pain

25 25 VNS expectations (2,8) Efficacy Symptom improvement ~33-50% >50% reduction in HAMD scores Benefits generally seen up to 12 months Additional benefits Enhanced neurocognitive functioning Improvement of pain symptoms Altered food cravings

26 26 Transmagnetic Stimulation (TIMS) (2,8) FDA approved in 2008 and 2013 External device: non-invasive procedure Focal, rapidly changing magnetic field induces an electrical current into a specific region of the brain Mechanism of action Unclear, but does increase brain-derived neurotrophic factor levels Adverse effects Mania Seizure (very rarely) Verbal retention

27 27 TIMS expectations (2,8) Efficacy 4 to 6 weeks of daily treatments Similar to that of ECT Younger patient > older patients Additional benefits Improved motor speed and reaction time Attention and processing speed Verbal fluency Memory and learning

28 End of the line? Not quite yet 28

29 29 Emerging pharmacological options (2) * Dopamine agonists Modulators of the hypothalamic-pituitaryadrenal (HPA) axis function Substance P (NK-1) antagonists Scopolamine S-Adenosylmethionine (SAMe) Glutamatergic modulation NMDA antagonists

30 30 NMDA antagonists (2) * Amantadine Pre-clinical studies appear positive Memantine Mixed results Riluzole Unclear results Ketamine Most promising of the NMDA antagonists

31 31 Ketamine (2,9,10) Structural derivative of phencyclidine NMDA-glutamate-receptor antagonist Allows glutamate to interact with AMPA Thought to be responsible for AD effects May also stimulate the following receptors: Opioid Dopamine Norepinephrine Serotonin Muscarinic

32 32 Patient selection (9,10)* Experimental therapy Only a handful of centers nationwide No defined criteria Generally considered as a last resort Informed consent crucial Unclear duration of action Repeat dosing not yet established Side effect profile

33 33 Potential adverse effects (9,10) Uncertain relief of depressive symptoms Usually within an hour of infusion Decreased suicidality Amnesia Psychosis Can be present for up to four hours post-infusion Very unsettling for family members Potential for self-harm Potential for staff harm

34 34 Ketamine infusion (9,10)* Done in a monitored area PACU, etc One hour infusion 0.5mg/kg Six hours of post-infusion monitoring Essential Discharge status depends on patient s mental state after monitoring Home or inpatient setting

35 35 Post-Test Approximately how many Americans will experience a bout of depression in their lifetime? million 2. 5 million million million

36 36 Post-Test Approximately how many Americans will experience a bout of depression in their lifetime? million 2. 5 million million million

37 37 Post-Test The most commonly used definition of treatmentresistant depression in the literature is a failure of how many antidepressant trials: 1. One 2. Two 3. Three 4. Four

38 38 Post-Test The most commonly used definition of treatmentresistant depression in the literature is a failure of how many antidepressant trials: 1. One 2. Two 3. Three 4. Four

39 39 Post-Test Which medication SHOULD to be held the evening prior to ECT? 1. Zolpidem 2. Eszopiclone 3. Zaleplon 4. Ramelteon

40 40 Post-Test Which medication SHOULD to be held the evening prior to ECT? 1. Zolpidem 2. Eszopiclone 3. Zaleplon 4. Ramelteon

41 41 Post-Test Which of the following is NOT an area of interest regarding antidepressant effects? 1. HPA axis modulators 2. SAMe 3. Metoprolol 4. Fish oil

42 42 Post-Test Which of the following is NOT an area of interest regarding antidepressant effects? 1. HPA axis modulators 2. SAMe 3. Metoprolol 4. Fish oil

43 43 Post-Test What factor will most likely limit the widespread use of ketamine? 1. Variable duration of effect 2. Adverse effect profile 3. Need for supervision post-infusion 4. Drug-drug interactions

44 44 Post-Test What factor will most likely limit the widespread use of ketamine? 1. Variable duration of effect 2. Adverse effect profile 3. Need for supervision post-infusion 4. Drug-drug interactions

45 45 References 1. Olchanski Natalia, Myers Michelle McInnis, Halseth Marily, et. al. The Economic Burden of Treatment-Resistant Depression. Clin Ther Apr; 35(4): Shelton Richard, Osuntokun Olawale, Heinloth Alexandra, et.al. Therapeutic Options for Treatment-Resistant Depression. CNS Drugs Feb;24(2): Rush AJ, Trivedi MH, Wisniewsk SRi, et al. Bupropion-SR, sertraline or venlafaxine XR after failure of SSRIs for depression. N Engl J Med Mar; 345 (12): Rush AJ, Trivedi MH, Wisniewsk SRi, et al. Acute and longerterm outcomes in depressed outpatient requiring one or several treatment steps: a STAR*D report. Am J Psychiatry Nov; 163 (11): Connolly K Ryan, Thase Michael E. If at first you don t Succeed: A Review of the Evidence for Antidepressant Augmentation, Combination and Switching Strategies. Drugs. 2011; 71 (1); 43-64

46 46 References 6. Kellner Charles, Greenberg Robert, Murrough James, Bryson Elaine, Briggs, Mimi, et al. ECT in Treatment-Resistant Depression. Am J Psychiatry Dec 1;169(12): D-methylfolate. In: Lexi-Drugs Online [Internet Database]. Hudson, OH: Lexi-Comp, Inc. Accessed 2013 Aug Moreinex Jared, McClintock Shawn, Holtzheimer Paul. Neurophsychological Effects of Neuromodulation Techniques for Treatment-Resistant Depression: A Review. Brain Stimul Jan; 4(1): Covver Jordan, Crawford Alexis Noble, Lowe Denise. Intravenous Ketamine for Treatment-Resistant Major Depressive Disorder. Ann Pharmacother. 2012; 46: Mathew Sanjay, Shah Asim, Lapidus Kyle, et. al. Ketamine for Treatment-Resistant Unipolar Depression. CNS drugs March 1; 26(3):

47 Questions? 47